Developmental Biology PDF

DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization ○ Our bodies constantly renew Topic Outline:...

DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization ○ Our bodies constantly renew Topic Outline: themselves, replacing skin cells and Introduction producing new blood cells. ○ Embryo ○ Stages of Development KEY FEATURES OF DEVELOPMENT ○ Key Features of Development Questions of Developmental Biology Animal development involves: ○ Source of Wonder Differentiation: The transformation of a single ○ Key Questions in Developmental Biology cell into various cell types. ○ Objectives of Developmental Biology Organogenesis: The construction of functional Specific Areas of Inquiry The Cycle of Life organs. ○ Embryogenesis Genotype to Phenotype: The process of An Example: A Frog’s Life transforming genetic information into physical ○ Gametogenesis and Fertilization ○ Cleavage and Gastrulation traits. ○ Organogenesis ○ Metamorphosis and Gametogenesis QUESTIONS OF DEVELOPMENTAL BIOLOGY Comparative Embryology SOURCE OF WONDER ○ Epigenesis and Preformationism Aristotle, the first known embryologist, said that An Overview of Early Development ○ Patterns of Cleavage wonder was the source of knowledge. ○ Gastrulation Animal development is a remarkable source of ○ The Primary Germ Layers and Early Organs wonder. ○ The Four Principles of Karl Ernst von Baer Keeping Track of Moving Cells: Fate Maps and Cell “How does a relatively homogeneous Lineages material transform into an orderly body?” ○ Fate Maps This question has intrigued humans since the ○ Direct Observation of Living Embryos dawn of self-awareness. ○ Dye Marking ○ Genetic Labeling ○ Transgenic DNA Chimeras KEY QUESTIONS IN DEVELOPMENTAL BIOLOGY Evolutionary Embryology Formation and Structure: How does the body ○ Embryonic Homologies form with its head always above the shoulders? Medical Embryology and Teratology ○ Genetic Malformations and Syndromes Why is the heart on the left side? How do simple ○ Disruptions And Teratogens tubes become complex structures like the brain Summary and spinal cord? Regeneration: Why can't we regrow limbs? INTRODUCTION Sex Determination: How do sexes develop EMBRYO different anatomies? The developing organism between fertilization Causal Networks: How can we explain a and birth. coherent causal network from genes to Must function as they are being built; respire functional organs? before having lungs, digest before possessing a Specific Questions: How does an XX genotype gut, and form bones while still being in a pulpy produce a female and an XY genotype produce state. a male? And how are globin genes expressed only in red blood cells and at specific times? THE STAGES OF DEVELOPMENT Multicellular organisms develop through a OBJECTIVES OF DEVELOPMENTAL BIOLOGY gradual process of change known as 1. Cellular Diversity and Order: How does a development. fertilized egg give rise to the adult body with its Begins with a single cell—the fertilized diverse cell types? egg—known as the zygote. 2. Continuity of Life: How does an adult body It does not stop at birth, or even at adulthood. produce another body? BSBIO 2-3 Lance Joshua P. Galvez | 1 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization anatomy, cancer research, neurobiology, immunology, SPECIFIC AREAS OF INQUIRY ecology, and evolutionary biology. Differentiation Understanding development is essential for A single cell gives rise to hundreds of different cell types, comprehending all other areas of biology. and so: How do identical sets of genes produce different THE CYCLE OF LIFE cell types? The sole way of getting from egg to adult is by Morphogenesis developing an embryo. It is where genotype Our differentiated cells are organized and not randomly (inherited genes) is translated into phenotype distributed, and so: (the adult organism). How do cells organize into functional structures? Growth EMBRYOGENESIS If each cell in our face were to undergo just one more The stages of development between fertilization cell division, we would be considered horribly and hatching are collectively called embryogenesis. malformed. And our arms are generally the same size on Each animal passes through similar stages of both sides of the body, and so: development, which are: How do cells know when to stop dividing? 1. Fertilization: The fusion of the gametes (sperm Reproduction and egg cells) initiates development. It also The sperm and egg are highly specialized cells, and only gives the embryo its genome that instructs the they can transmit the instructions for making an embryo to develop in a manner similar to that of organism from one generation to the next, and so: its parents. How are germ cells specialized for transmitting 2. Cleavage: A series of extremely rapid mitotic genetic information? divisions immediately following fertilization. The Regeneration zygote cytoplasm is divided into numerous Some organisms can regenerate every part of their smaller cells— the blastomeres—which form a bodies. While mammals are generally poor at sphere called a blastula. regeneration, there are some cells in our bodies that are 3. Gastrulation: A series of extensive cell able to form new structures even in adults, and so: rearrangements and forms three germ layers How do some organisms regenerate parts, and (endoderm, ectoderm, mesoderm). At this point, can we harness this ability? the embryo is in the gastrula stage. Environmental Integration 4. Organogenesis: The interaction between cells Organism development is influenced by environmental of germ layers to form tissues and organs. cues, such as temperature, bacteria, and chemicals, Certain cells become precursors of blood, which can affect sex, reproduction, and cause lymph, pigment, and gametes by undergoing malformations. So: long migrations from their origin to their final How does the environment influence location. development? 5. Birth or Hatching: The organism is either born Evolution or emerges from the egg. Evolution involves inherited changes of development 6. Metamorphosis: The process in which various which occurs over many generations, so: organisms undergo in order to become sexually How do changes in development create new mature. In most animals, a young organism is body forms? called a larva. 7. Gametogenesis: A group of cells are set aside IMPORTANCE OF DEVELOPMENTAL BIOLOGY for reproductive function which becomes the The questions asked by developmental precursors to gametes for the next generation. biologists are crucial in various fields, including Collectively, they are called germ cells and molecular biology, physiology, cell biology, genetics, migrate to the gonads where they differentiate BSBIO 2-3 Lance Joshua P. Galvez | 2 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization during the development of gametes, or Frog Fertilization gametogenesis. Somatic cells form other parts Most species of frogs fertilize externally. of the body, while germ cells ensure The male frog grabs the female’s back and reproduction. After fertilization, the life cycle fertilizes the eggs as the female releases them. continues as the adult organism eventually dies. AN EXAMPLE: A FROG’S LIFE Some species lay their eggs in pond vegetation, where the egg jelly sticks to the plants and anchors the eggs. In other species, the eggs simply float into the center of the pond without support. CLEAVAGE AND GASTRULATION Cleavage During cleavage, the volume of the frog egg stays the same, but it is divided into tens of GAMETOGENESIS AND FERTILIZATION thousands of cells. Life cycles are usually influenced by environmental factors (e.g., tadpoles wouldn't survive if they hatched in the fall when their food is dying). In most frogs, gametogenesis and fertilization are seasonal events. A combination of photoperiod (hours of daylight) and temperature informs the pituitary gland of the mature female frog that spring has arrived. Gastrulation Pituitary secretions then cause the eggs and Begins at a point 180° opposite the point of sperm to mature. sperm entry. Starts with a formation of a dimple called Fertilization blastopore which marks the future dorsal side It serves two purposes: of the embryo and expands to become a ring. 1. Sex (genetic recombination). ○ Cells migrating through the blastopore 2. Reproduction (generation of a new individual). into the embryo’s interior become the mesoderm and endoderm. The genomes of the haploid male and female ○ Cells remaining outside become the pronuclei combine to form a diploid zygote ectoderm, and this outer layer expands nucleus. to enclose the entire embryo. The entry of the sperm also initiates the movement of cytoplasm inside the fertilized egg, Germ Layers and Their Roles which is crucial in determining the frog's three Ectoderm: Precursor of the epidermis, brain, body axes. and nerves (outside the embryo). BSBIO 2-3 Lance Joshua P. Galvez | 3 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization Endoderm: Precursor of the gut lining and respiratory systems (deep inside the embryo). Mesoderm: Precursor of connective tissue, muscle, blood, heart, skeleton, gonads, and kidneys (between the ectoderm and endoderm). ORGANOGENESIS It begins when the dorsal mesoderm cells condense to form a rod of cells called the Neurons connect to muscles and other neurons, notochord which release chemical signals that the gills form, and the larva is ready to hatch influence the fate of the ectodermal cells from its egg. above them. The hatched tadpole will feed for itself once the yolk supplied by its mother is depleted. Formation of the Nervous System Instead of forming epidermis, the ectodermal cells above the notochord are instructed to become the cells of the nervous system which change shape and rise from the round body. METAMORPHOSIS AND GAMETOGENESIS Metamorphosis The fully aquatic tadpole larva undergoes significant changes to become a land-dwelling adult frog. These changes include: At this stage, the embryo is called the neurula. Limb Development: Hindlimbs and forelimbs The neural precursor cells elongate, stretch, and develop for locomotion as the paddle tail fold into the embryo to form the neural tube. recedes. The future epidermal cells of the back cover the Skull Transformation: The cartilaginous neural tube at this stage. tadpole skull is replaced by a bony adult skull. Mouth and Jaw Changes: Horny teeth Development of Somite disappear, and the mouth and jaw adapt for a Once the neural tube has formed, it—along with carnivorous diet. the notochord—induces changes in the Digestive System Adjustment: The intestine surrounding regions. shortens to accommodate a more carnivorous Mesodermal tissue adjacent to the neural tube diet. and notochord segments into somites, which Respiratory System Changes: Gills regress, are the precursors of back muscles, spinal and lungs enlarge. vertebrae, and dermis. Tadpole Development The embryo develops a mouth and an anus, elongating into the familiar tadpole structure. BSBIO 2-3 Lance Joshua P. Galvez | 4 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization Comparative Anatomy and Evolutionary Questions Questions also arise about how the tissues that form a bird’s wing relate to those that form a fish fin or a human hand. These inquiries are rooted in developmental biology and its embryological heritage. Contributions of Aristotle to Embryology He conducted the first study of comparative developmental anatomy from The Generation of Animals (ca. 350 BCE). He observed variations in life cycles and noted different forms of birth. Figure 1.3. Metamorphosis of the frog. (A) Huge changes are obvious ○ Oviparity: birth from eggs as seen in when one contrasts the tadpole and the adult bullfrog. Note especially the differences in jaw structure and limbs. (B) Premetamorphic tadpole. birds, frogs, and most invertebrates. (C) Prometamorphic tadpole, showing hindlimb growth. (D) Onset of ○ Viviparity: live birth, as in placental metamorphic climax as forelimbs emerge. (E,F) Climax stages. mammals. ○ Ovoviviparity: production of egg that Hormonal Regulation hatches inside the body, as in certain Thyroid hormones initiate amphibian reptiles and sharks. metamorphosis. He identified the two major cell division patterns The speed of metamorphosis is influenced by in embryos. environmental factors. For example, in ○ Holoblastic: the entire egg is divided temperate regions, frogs must metamorphose into smaller cells, as in frogs and before ponds freeze in winter. mammals. ○ Meroblastic: only part of the egg Gametogenesis becomes the embryo, while the rest (the It begins as metamorphosis ends. yolk) provides nutrition, as in chicks. This process can take a significant amount of He also discovered the functions of the placenta time. In Rana pipiens, it takes three years for and umbilical cord in mammals. eggs to mature in the female's ovaries. But sperm development is quicker, and male Contributions of William Harvey Rana can often become fertile shortly after He concluded in 1651 that all animals originate metamorphosis. from eggs. “Ex ovo omnia” is his famous motto that rejected Maturation and Fertilization the idea of spontaneous generation. Germ cells must become competent to He was the first to observe the blastoderm in complete meiosis before they can mature. After the chick embryo, where the yolk-free cytoplasm meiosis, mature sperm and egg nuclei can unite gives rise to the embryo. in fertilization, restoring the diploid ○ Harvey also noticed the formation of chromosome number and initiating the events blood tissue islands before the heart that lead to development and the continuation of develops. the life cycle. ○ He suggested that amniotic fluid might act as a shock absorber for the embryo. COMPARATIVE EMBRYOLOGY “Since a fertilized cell has no heart, does it form the same way in both insects and vertebrates?” BSBIO 2-3 Lance Joshua P. Galvez | 5 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization Embryology and Microscopy limit was known for the size of Progress in embryology was slow until the preformed organisms. invention of the microscope allowed for detailed observations. Challenges to Preformationism In 1672, Marcello Malpighi published the first Intergenerational Variations microscopic account of chick development. ○ Why does a white and black parent ○ He identified critical structures like the produce an offspring with neural groove (precursor of the neural intermediate skin color? tube), muscle-forming somites, and ○ Joseph Kölreuter (1766) produced the first circulation of arteries and hybrid tobacco plants with traits from veins to and from the yolk. both parent species. EPIGENESIS AND PREFORMATIONISM Revival of Epigenesis One of the great debates in embryology began with Kaspar Friedrich Wolff revived epigenesis by Marcello Malpighi: observing chick embryos. “Are organs formed de novo ("from scratch") in He demonstrated that embryonic parts (like the each generation, or are the organs already heart, intestine, and blood vessels) develop present in miniature form within the egg or from tissues that do not have counterparts in sperm?” the adult organism. Wolff (1767) confidently stated that his findings Epigenesis supported epigenesis, though he postulated an This view holds that the organs of an embryo unknown force, the vis essentialis ("essential form anew during development. force"), to explain how embryonic development It was supported by both Aristotle and Harvey. is organized. Preformationism Reconciliation Between Epigenesis and Suggests that organs of an adult are prefigured Preformationism in miniature within the sperm or egg. It says that Proposed by Immanuel Kant and Johann organisms are not “constructed” but rather Friedrich Blumenbach. “unrolled” or “unfurled.” Blumenbach introduced the concept of a Malpighi showed that the unincubated chick egg mechanical, goal-directed force called already had a great deal of structure. This led Bildungstrieb ("developmental force"). him to support preformationism rather than He claimed this force was observable, as epigenesis. demonstrated by the regeneration of hydra when amputated (a form of reorganization of Support for Preformationism existing elements). From 18th-century science, religion, and The idea that epigenetic development is philosophy: directed by preformed instructions is close to ○ Embryonic development merely modern biology’s view: most of the involved the growth of existing instructions for forming an organism are structures, not the formation of new already present in the fertilized egg. ones. ○ Another generation was thought to exist AN OVERVIEW OF EARLY DEVELOPMENT in a prefigured state within the germ PATTERNS OF CLEAVAGE cells of the current generation. E. B. Wilson noted in 1923 the complexity of cell ○ The lack of cell theory at the time division, particularly during cleavage, despite its allowed for this view to persist, as no seemingly simple task. BSBIO 2-3 Lance Joshua P. Galvez | 6 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization Cleavage in Cells Blastomeres: cells in the cleavage-stage. In most species (excluding mammals), the initial rate of cell division and the placement of blastomeres are controlled by proteins and mRNAs stored in the oocyte. Only later do these processes come under the control of the newly formed organism’s genome. ○ In this initial phase, the cytoplasmic volume does not increase, and the zygote cytoplasm is divided into progressively smaller cells. Cleavage occurs rapidly in most invertebrates, likely as an adaptation to generate many cells quickly. This process restores the somatic ratio of nuclear volume to cytoplasmic volume. Parameters Determining Cleavage Patterns 1. Amount and distribution of yolk protein within the cytoplasm, which influences the location and size of blastomeres. 2. Factors in the egg cytoplasm that affect the angle of the mitotic spindle and the timing of its formation. 1. Holoblastic Cleavage: occurs in isolecithal Yolk generally inhibits cleavage. When one eggs (have sparse, equally distributed yolk), pole of the egg is yolk-free, cell divisions occur where the cleavage furrow extends through the faster there than at the opposite pole. entire egg. There are four major cleavage ○ The vegetal pole is the yolk-rich side, patterns: while the animal pole has less yolk and ○ Radial usually contains the zygote nucleus. ○ Spiral ○ Bilateral Types of Cleavage Based on Yolk Distribution ○ Rotational Although yolk distribution is a major factor 2. Meroblastic Cleavage: occurs in insect, fish, influencing cleavage patterns, closely related species reptile, and bird eggs, where only part of the can have different cleavage patterns adapted to different cytoplasm is cleaved due to large yolk environments. accumulations. ○ In birds and fish, only a small area of the egg is free of yolk (telolecithal), leading to discoidal cleavage in a small disc of cytoplasm. ○ In insect eggs, yolk is in the center (centrolecithal), and cytoplasm divides only around the periphery (superficial cleavage). BSBIO 2-3 Lance Joshua P. Galvez | 7 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization GASTRULATION: ○ Delamination “THE MOST IMPORTANT TIME IN YOUR LIFE” ○ Epiboly According to embryologist Lewis Wolpert (1986), "It is not birth, marriage, or death, but Establishment of Body Axes gastrulation which is truly the most important time in Gastrulation also establishes three critical axes your life." for the organism's body: Gastrulation is a defining feature of animal development, as plants and fungi do not undergo this process. Purpose of Gastrulation During gastrulation, cells of the blastula move to new positions. This establishes the multilayered body plan of the organism. ○ Anterior-posterior axis: Extends from This process positions the cells that will form the head to tail (or mouth to anus in endodermal and mesodermal organs inside organisms without heads or tails). the embryo, while the cells that will form the ○ Dorsal-ventral axis: Extends from back skin and nervous system are spread over its (dorsum) to belly (ventrum). outer surface. ○ Right-left axis: Divides the two lateral To produce the three germ layers known as sides of the body. outer ectoderm, inner endoderm, and These axes are essential for positioning interstitial mesoderm. organs. For example, in most humans, the heart is on the left side, while the liver is on the right. Types of Cell Movement The embryo somehow knows where specific organs should be located. NAMING THE PARTS: THE PRIMARY GERM LAYERS AND EARLY ORGANS The end of preformationism came in the 1820s, thanks to new staining techniques, improved microscopes, and reforms in German universities. These advancements enabled scientists to observe the epigenesis of anatomical structures. EARLY DISCOVERIES IN EMBRYOLOGY Three influential figures in early embryology were Christian Pander, Heinrich Rathke, and Karl Ernst von Baer. These three friends, all born in the Gastrulation involves complex movements of Baltic region and trained in northern Germany. the entire embryo, requiring precise coordination between various cell migrations. Discoveries of Christian Pander Although patterns of gastrulation vary across Christian Pander, while studying the chick the animal kingdom, all are combinations of embryo, discovered that the embryo was five basic cell movements: organized into three germ layers: ○ Invagination ○ Involution ○ Ingression BSBIO 2-3 Lance Joshua P. Galvez | 8 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization ○ Ectoderm: Generates the outer layer of the embryo, producing the epidermis (skin surface) and forming the brain and nervous system. ○ Endoderm: Becomes the innermost layer, producing the epithelium of the Figure 1.3. Evolution of pharyngeal arch structures in the vertebrate digestive tube and its associated head. (A) Pharyngeal arches in the embryo of the salamander Ambystoma mexicanum. (B) In adult fish, pharyngeal arch cells form organs, including the lungs. the hyomandibular jaws and gill arches. (C) In amphibians, birds, and ○ Mesoderm: Lies between the reptiles (a crocodile is shown here), these same cells form the ectoderm and endoderm, generating quadrate bone of the upper jaw and the articular bone of the lower jaw. the blood, heart, kidneys, gonads, (D) In mammals, the quadrate has become internalized and forms the incus of the middle ear. The articular bone retains its contact with the bones, muscles, and connective tissues. quadrate, becoming the malleus of the middle ear. He also discovered that the germ layers do not form their respective organs autonomously. THE FOUR PRINCIPLES OF KARL ERNST VON BAER Induction is required for them to develop Von Baer expanded Pander’s studies of the properly, a process where they interact with chick embryo and discovered that all vertebrate embryos each other. follow a common developmental pattern. ○ No vertebrate tissue can construct He discovered: the notochord, a mesodermal organs by itself—it must interact with rod that divides the embryo into right and left other tissues. halves, guiding the formation of the nervous system from the ectoderm; and the mammalian Contributions of Heinrich Rathke egg, the long-sought, minute cell crucial for He focused on the development of complex understanding reproduction and development. structures in vertebrates, such as the skull, excretory systems, and respiratory systems. He showed that these structures become more complex during development and follow different trajectories in different vertebrate classes. He was the first to identify pharyngeal arches, which develop into different structures depending on the organism. For example: ○ In fish, the arches become gill supports. ○ In mammals, they develop into jaws and ears, among other structures. BSBIO 2-3 Lance Joshua P. Galvez | 9 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization Von Baer’s Laws 4. Therefore, the early embryo of a higher 1. The general features of a large group of animal is never like a lower animal, but only animals appear earlier in development than like its early embryo. do the specialized features of a smaller ○ As development advances, each group. embryo grows more distinct from other ○ Early in development, embryos from species and becomes more specialized different species exhibit similar to its final adult form. characteristics. ○ For instance, even though mammalian, bird, and reptile embryos may resemble each other early on, they eventually form features unique to their species (e.g., feathers in birds, fur in mammals). KEEPING TRACK OF MOVING CELLS: FATE MAPS AND CELL LINEAGES By the late 1800s, it had been conclusively demonstrated that the cell is the basic unit of all anatomy and physiology. Embryologists began to base ○ These general features (e.g., presence their field on the cell as well. of a neural tube or pharyngeal arches) However, unlike those who studied the adult are established before the organism, developmental anatomists found that cells in species-specific traits emerge. the embryo do not “stay put.” 2. Less general characters develop from the Embryonic cells do not remain in one place, more general, until finally the most nor do they keep the same shape. specialized appear. ○ As development progresses, species Types of Embryonic Cells start to diverge, and specific features Epithelial cells: Tightly connected to one unique to a particular organism (e.g., the another in sheets or tubes. wings of a bird or the fins of a fish) begin Mesenchymal cells: Unconnected or loosely to form. connected and can operate as independent ○ For example, even though many units. vertebrates initially have pharyngeal arches, these later form gills in fish but Morphogenesis and Cellular Processes jaws and ears in mammals. The way epithelial and mesenchymal cells are 3. The embryo of a given species, instead of organized in the embryo influences how the embryo passing through the adult stages of lower develops its shape and structure. animals, departs more and more from them. 1. Direction and Number of Cell Divisions - The ○ Von Baer opposed the idea that number and orientation of cell divisions vary embryos of more complex animals go between different organisms. For example: through the adult stages of simpler ○ The faces of a German shepherd and a animals (like fish or amphibians). poodle are made from the same cell ○ He argued that embryos follow their own types, but the number and orientation developmental paths, which diverge of their cell divisions differ. from one another rather than ○ The legs of a dachshund are shorter progressing through a linear evolution of than those of a taller dog like a German simpler organisms' adult forms. shepherd due to fewer cell divisions. BSBIO 2-3 Lance Joshua P. Galvez | 10 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization 2. Cell Shape Changes - Cell shape change is a ○ Matrices made by other cells can critical feature of development. For example: prohibit migration, establishing "paths ○ Changing the shapes of epithelial cells and guiderails" for migrating cells. often creates tubes out of sheets (such as when the neural tube forms). FATE MAPS ○ A change from epithelial to In a dynamic situation such as embryonic mesenchymal allows cells to migrate development, one of the most important tasks of from the epithelial sheet (such as in the descriptive embryology is tracing cell lineages. formation of muscle cells). In many organisms, it is not always possible to ○ This epithelial-to-mesenchymal resolve individual cells. However, researchers can transition also occurs in cancer, where it label groups of embryonic cells to track what those enables cancer cells to migrate and groups become in the adult organism. spread from the primary tumor to new sites. Importance of Fate Maps 3. Cell Migration - Cells must move to their By compiling these studies, researchers can appropriate locations for proper development. create a diagram, known as a fate map, which For instance: essentially “maps” larval or adult structures onto the ○ Germ cells must migrate into the region of the embryo from which they originated. developing gonad. Fate maps provide a critical foundation for ○ Primordial heart cells meet in the middle experimental embryology. of the vertebrate neck and migrate to They offer valuable insights into which portions the left part of the chest. of the embryo develop into specific larval or 4. Cell Growth - Cells can change in size. This is adult structures. especially clear in germ cells: ○ The sperm eliminates most of its cytoplasm and becomes smaller. ○ The egg conserves and adds cytoplasm, becoming comparatively large. ○ Many cells undergo asymmetric division, where one big cell and one small cell are formed, each possibly having a completely different fate. 5. Cell Death (Apoptosis) - Cell death is a crucial part of development. For example: ○ Embryonic cells that form the webbing between our toes and fingers die before birth. ○ The cells in our tails also die. ○ Apoptosis forms the orifices of the Advances in Fate Map Technology mouth, anus, and reproductive glands. Fate maps can be generated through several 6. Changes in Cell Membrane Composition or methods, and the technology for doing so has Secreted Products - The cell membrane and advanced significantly in recent years. secreted products influence neighboring cells. For example: The ability to follow cells using molecular dyes ○ Extracellular matrices secreted by one and computer imaging has revolutionized our set of cells can allow the migration of understanding of the origins of several cell neighboring cells. types. BSBIO 2-3 Lance Joshua P. Galvez | 11 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization This new technology has even altered our views He then cut chips from the ends of the dyed on where heart cells originate. agar and placed them on a frog embryo. After the dye stained the cells, the agar chips Challenges in Mapping Mammalian Embryos were removed, allowing him to follow the Mammalian embryos are particularly movements of the stained cells within the challenging to map due to their development inside embryo. another organism. Researchers are continuously working on constructing, refining, and even debating the fate maps of mammalian embryos. DIRECT OBSERVATION OF LIVING EMBRYOS Some embryos have relatively few cells, and in some cases, the cytoplasms of their early blastomeres contain differently colored pigments. Researchers can use a microscope to trace the descendants of a particular cell as it forms specific organs. E.G. Conklin was able to trace the fate of each early cell in the tunicate Styela partita (sea squirt). ○ The muscle-forming cells of the Styela Limitations and Solutions with Dye Marking embryo were always yellow, and this One problem with vital dyes is that as they pigment was derived from a region of dilute with each cell division, they become harder to cytoplasm found in a specific pair of detect. blastomeres at the 8-cell stage. Solution: To use fluorescent dyes which are ○ When this pair of blastomeres (which intense enough to remain detectable even after Conklin’s fate map showed would many cell divisions. produce tail musculature) was ○ For example, Fluorescein-conjugated removed, the result was larvae without dextran can be injected into a single tail muscles, confirming the accuracy cell of an early embryo, and its of Conklin’s fate map. descendants can still be observed under ultraviolet light. DYE MARKING Most embryos do not have cells with naturally different colors. In the early 20th century, Vogt (1929) developed a technique to trace the fates of different GENETIC LABELING areas of amphibian eggs by applying vital dyes to the One way to permanently mark cells and follow regions of interest which stain cells but do not kill them. their fates is by creating embryos where cells have Vogt used a technique where he mixed dyes different genetic constitutions. A notable example of with agar and dried the mixture on a microscope this technique is the construction of chimeric embryos slide. BSBIO 2-3 Lance Joshua P. Galvez | 12 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization (embryos made from tissues of more than one genetic express a fluorescent protein like green fluorescent source). protein (GFP). Chick-quail chimeras are created by grafting A gene modified this way is called a transgene quail cells into a chick embryo while the chick is still in because it contains DNA from another species. the egg. When infected cells are transplanted into a Chicks and quail embryos develop similarly, wild-type host, only the donor cells will express allowing quail cells to integrate into the chick GFP, emitting a visible green glow. and contribute to various organs. After the chick hatches, quail cells can be found Transgenic labeling can provide a highly at specific sites, depending on where the graft precise map of the developing body. For example: was placed. Freem et al. (2012) used transgenic techniques to Quail cells differ from chick cells in important study the migration of neural crest cells to the gut of ways, such as in species-specific proteins that chick embryos. form the immune system. Neural crest cells form the neurons that These quail-specific proteins make it possible to coordinate peristalsis (the muscular contractions detect individual quail cells, even when they are that move waste through the gut). hidden within a larger population of chick cells. The parents of the GFP-labeled chick embryo This allows for the creation of fine-structure were infected with a virus carrying an active maps of the chick brain and skeletal system. GFP gene. This virus was passed to the chick embryo, making every cell in the embryo glow Chimeras have confirmed the extensive green under ultraviolet light. migrations of neural crest cells during vertebrate The neural tube and neural crest were then development: Mary Rawles (1940) showed that the transplanted from a GFP-transgenic embryo pigment cells (melanocytes) in chicks originate in the into a similar region of a normal chick embryo. neural crest. A day later, GFP-labeled cells were observed She transplanted neural crest tissue from a migrating into the stomach region. After 7 days, pigmented strain of chickens into an the entire gut showed GFP staining, reaching unpigmented strain. The migrating pigment the anterior hindgut. cells entered the epidermis and eventually the feathers. EVOLUTIONARY EMBRYOLOGY Ris (1941) confirmed that the retinal pigment Charles Darwin's theory of evolution formed within the retina itself and did not rely reshaped comparative embryology and provided it with a on migrating neural crest cells. new focus. After reading Johannes Müller’s summary of This was further validated with chick-quail von Baer’s laws in 1842, Darwin recognized that chimeras, where quail neural crest cells embryonic similarities could strongly support the produced their own pigment in the chick genetic connectedness of different animal groups. feathers. Darwin concluded: “Community of embryonic structure reveals community of descent.” TRANSGENIC DNA CHIMERAS Darwin’s interpretation of von Baer’s laws In many animals, creating chimeras from two established the idea that relationships between species is challenging but can be overcome by groups could be understood by finding common transplanting cells from a genetically modified embryonic or larval forms. organism. The genetic modification can then be traced only in the cells that express it. Pre-Darwinian Discoveries in Embryology A common method involves infecting the cells of Larval forms were used in taxonomic an embryo with a virus whose genes are modified to classification: BSBIO 2-3 Lance Joshua P. Galvez | 13 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization In the 1830s, J. V. Thompson demonstrated produce structures that help animals that larval barnacles were almost identical to adapt to specific conditions. larval shrimp, correctly classifying barnacles as arthropods rather than mollusks (Figure 1.17; EMBRYONIC HOMOLOGIES Winsor 1969). Homologous structures: Organs with Darwin celebrated this finding, stating that “a underlying similarities due to being derived glance at the larva shows in an unmistakable from a common ancestral structure. manner” that barnacles are crustaceans, ○ The wing of a bird and the arm of a contrary to Cuvier's view. human are homologous, both having evolved from the forelimb bones of a Kowalevsky’s Discovery and Darwin's Support common ancestor. Their respective Alexander Kowalevsky (1871) made another parts are also homologous. important discovery: Tunicate larvae have a notochord and pharyngeal pouches that originate from the same germ layers as in fish and chicks. Kowalevsky concluded that invertebrate tunicates are related to vertebrates. Darwin endorsed Kowalevsky’s discovery, writing in The Descent of Man (1874): “If we may rely on embryology, ever the safest guide in classification, it seems that we have at last gained a clue to the source from which the Vertebrata were derived.” Embryonic Evidence of Descent Darwin also noted that embryonic organisms sometimes form structures inappropriate for their adult form, but which demonstrate their relatedness to other animals. Examples include: Eyes in embryonic moles. Pelvic bone rudiments in embryonic snakes. Teeth in baleen whale embryos. Development and Adaptation Darwin observed that adaptations that enable an Analogous structures: Organs that are similar organism to survive in its environment often develop late because they perform a similar function but in the embryo. He noted that differences among do not arise from a common ancestor. species within genera become more pronounced as ○ The wing of a butterfly and the wing of a development continues, in line with von Baer’s laws. bird are analogous. They share a Darwin recognized two approaches to descent common function but did not arise from with modification: the same ancestral structure. ○ Emphasizing common descent by highlighting embryonic similarities Homology and Levels of Organization between animal groups. Homology must be examined at the level of ○ Emphasizing modifications to show organization being compared. For example: how development has been altered to Bird and bat wings are homologous as forelimbs but not as wings. Birds and BSBIO 2-3 Lance Joshua P. Galvez | 14 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization mammals share a common ancestor with forelimb bones, but bird wings evolved from MEDICAL EMBRYOLOGY AND TERATOLOGY ancestral reptiles, while bat wings evolved Physicians are interested in embryos to address from non-winged mammals. practical medical concerns. Between 2% and 5% of human infants are born Evolutionary Change and Development with observable anatomical abnormalities Evolutionary changes are based on such as: missing limbs or digits, cleft palate, and developmental changes. Bat wings are a good malformations in eyes or heart valves. example of how developmental processes alter Some birth defects are caused by mutant structures: genes or chromosomal issues, while others Rapid growth is maintained in the cartilage are due to environmental factors. forming the fingers. The study of birth defects can shed light on Cell death that normally occurs in the webbing how the human body is normally formed. between the fingers is prevented, creating the wing membrane. GENETIC MALFORMATIONS AND SYNDROMES Abnormalities caused by genetic events like gene mutations or chromosomal issues are called malformations. A syndrome occurs when two or more malformations occur together. Holt-Oram syndrome is an autosomal dominant condition where children have both a For example, mice (like most mammals) begin malformed heart (due to improper growth of the development with webbing between their digits, septum) and absent wrist or thumb bones. which is important for anatomical distinctions between fingers. However, genetic signals DISRUPTIONS AND TERATOGENS cause the webbing to die once its function is Disruptions are developmental abnormalities complete, leaving free digits. caused by external agents (chemicals, viruses, In bats, the genes that are active in the webbing radiation). The agents responsible are called teratogens encode proteins to prevent cell death and (from Greek, meaning "monster-formers"), and the promote finger elongation. study of how these agents disrupt development is called teratology. Teratogens include: alcohol, retinoic acid Artificial Selection and Genetic Mutations (used to treat acne), heavy metals (e.g., mercury, lead, Darwin observed artificial selection in pigeon selenium), which can affect brain development. and dog breeds. Dachshunds were bred for their short legs, Public Awareness of Teratogens which were useful for hunting badgers in In the early 1960s, teratogens gained public underground burrows. attention due to the drug thalidomide, prescribed as a This trait results from a mutation that produces sedative for pregnant women. In 1961, Lenz and an extra copy of the Fgf4 gene, which tells McBride independently found that thalidomide caused a cartilage precursor cells to stop dividing earlier dramatic increase in a previously rare syndrome, than in other dogs, leading to shorter legs. including phocomelia, where the long bones of the Similarly, long-haired dachshunds have a limbs are deficient or absent. A single tablet of mutation in the Fgf5 gene, which controls hair thalidomide was enough to cause deformities. More than production and allows each follicle to make a 7,000 infants were affected, with symptoms such as: longer hair shaft. Deformed limbs Mutations in developmental genes can generate Heart defects selectable variation. Missing external ears Malformations of intestines BSBIO 2-3 Lance Joshua P. Galvez | 15 DEVELOPMENTAL BIOLOGY Mr. Arnel O. Rendon | Chapter 1 - Making New Bodies: Mechanisms of Developmental Organization 7. Cell migration and differentiation: Some cells Nowack (1965) documented that thalidomide stay in place to differentiate, while migratory was only teratogenic between days 34–50 after cells (e.g., neural crest, germ cells) move to the last menstruation (i.e., 20–36 days new locations to differentiate. post-conception), with different effects 8. Embryonic structure and descent: Darwin's depending on timing: idea that similar embryonic structures indicate ○ 34–38 days: absence or deficiency of common ancestry. ear components. 9. Homologous vs. analogous structures: ○ Upper limb malformations occur earlier Homologous structures share a common than lower limb issues because arms ancestral origin, while analogous structures develop before legs. share a similar function without a common origin. Modern Medical Integration 10. Congenital anomalies: These can be caused The integration of anatomical information about by genetic factors (mutations, aneuploidies) or congenital malformations with our knowledge of environmental agents (chemicals, viruses, developmental genes is helps us to: radiation). Identify the genes responsible for inherited 11. Teratogens: Environmental compounds that malformations. disrupt development, acting at specific times Understand which developmental steps are when certain organs are forming, similar to disrupted by specific teratogens. genetic malformations that occur when cell communication is disrupted. SUMMARY 1. Life cycle as a central unit in biology: The basic animal life cycle involves stages from fertilization to senescence, not just the adult form. 2. Gametogenesis: Germ cells undergo meiosis, leading to the formation of sperm or eggs, which unite during fertilization to begin development. 3. Epigenesis: Organisms are created anew each generation from the relatively disordered cytoplasm of the egg. 4. Preformation in genetic instructions: The fertilized egg inherits genetic instructions that guide organ formation and allow responses to environmental stimuli. 5. Germ layers and organ systems: The three germ layers—ectoderm, mesoderm, and endoderm—each give rise to specific organ systems. 6. Von Baer’s principles: General features of animals appear earlier in embryos than specialized features. Embryos of different species diverge from each other during development. BSBIO 2-3 Lance Joshua P. Galvez | 16