Chapter 1 Developmental Anatomy: An Overview PDF

2024 Chapter 1 Chapter 1: Developmental Anatomy: An Overview Key terms and concepts: Developmental Anatomy Developmental Biology Congenital Genetic Teratogen...

2024 Chapter 1 Chapter 1: Developmental Anatomy: An Overview Key terms and concepts: Developmental Anatomy Developmental Biology Congenital Genetic Teratogen Model organism Knockout mouse Critical periods Learning objectives: By the end of this unit, you should be able to: 1. Define the key terms and concepts listed above 2. Think of at least one reason why an understanding of developmental anatomy will enhance your practice of veterinary medicine. 3. Understand why experimental findings from model organisms, including flies and mice, are relevant to your training and practice. 4. Understand the differences and similarities between congenital and genetic defects. 5. Propose at least one reason why a “critical period” for a tissue or organ would be critical. I. Historical context A. “How are you?” The question of how animals develop has been studied and debated by some of the most prolific scientists and philosophers throughout history including Aristotle, Immanuel Kant, Charles Darwin, and Leonardo Da Vinci. See Chapter 1 of “Essentials of Domestic Animal Embryology” by Hytell if you are interested in learning more about the fascinating history of embryology. II. Overview of Vertebrate Embryonic Structure A. In this course and many others, we will often speak of the general patterns of structure and development without always discussing each species separately, since there are many more similarities than differences among domestic mammals. Many problems, such as how to structure a limb to bear weight efficiently, seem to have been solved once by nature, then adapted for various specialized needs such as running or digging. The differences among species are usually due to small adjustments in the proportions of body parts, not to radical changes in the principles of their construction. Evolution does not reinvent complex processes—it fine tunes existing systems to fit variations in the environment, using a common genetic toolbox. Thinking of species as variations on a theme helps us learn concepts that we can apply to animals we rarely deal with, instead of attempting to memorize every detail of every animal. B. Early Vertebrates that look nothing alike as adults begin as very similar appearing embryos. Particularly at early stages, we can describe development in a general way that will apply to most vertebrate embryos. Only later in development do the specific features of that type of animal appear. As development proceeds, the embryos of different species look less and less like each other. 1  2024 Chapter 1 C. Our understanding of developmental biology and embryology is based largely on the study of model organisms. Several organisms have been extensively used in the study of developmental biology; the chick, the mouse, the fish (zebrafish), the frog (Xenopus laevis) as well as several invertebrate species. Most recent studies have utilized these model organisms. Classical embryology additionally utilized the pig and the sheep as model organisms, and other species have been examined to less complete degrees. Thus, as we learn about developmental biology, we will often be learning about processes that have been described in mice or other model organisms and which we extrapolate to other species. The title of this course is (of course) Developmental Anatomy, which is the study of animal development. Throughout this semester, we will also address the “how” of developmental anatomy. This is the domain of Developmental Biology, which is the study of the molecular, cellular and and morphological mechanisms that regulate animal development. D. Embryos may contain structures which are temporary and useless to the adult, but reflect that animal’s evolutionary relatedness to other animals. For example, embryonic fish and amphibians have a very basic kidney called the “pronephros.” During development, it is replaced by a more complex adult kidney called the “mesonephros.” But domestic mammals need to conserve water, so neither of these versions works for them. The mammalian adult “metanephros” is complex and efficient at retaining water. Surprisingly, though, the metanephros of the mammalian embryo is preceded by first the pronephros, then the mesonephros before the final version replaces them both. E. If you've previously taken a course in developmental biology, you may have spent a lot of time discussing fruit flies, sea urchins, amphibians, chicks and other interesting creatures. This course will primarily concentrate on mammals, so you will find some important differences with what you may have previously learned. We owe much of what we know about mammalian development to the study of non-mammalian species, but be ready for differences! III. Genetic vs Environmental impact on development; congenital malformations A. Alterations in signals coming from the environment as well as alterations in genes (mutations) can impact many developmental processes in mammals. 1. Most processes in development are sensitive to both genetic changes and environmental conditions. B. Congenital malformations are conditions present at birth (although not always recognized at birth) that result from disruption in developmental processes and often adversely impact the animal’s health. 1. Congenital defects can range in severity from minimal to lethal. 2. It is estimated that about 10% of all developmental malformations are caused by environmental factors and another 20% by genetic and chromosomal factors. The remaining 70% are presumably caused by a complex interaction of several genetic and environmental factors. 3. Determining whether the cause of a malformation is genetic or environmental is sometimes possible and extremely important, so that steps can be taken to prevent reoccurrence. 2 2024 Chapter 1 4. Genetic malformations are conditions caused by one or more abnormalities in the genome. a. Certain species and breeds have a high incidence of particular genetically transmitted traits. Certain mutations are more common in particular breeds or families and can give rise to genetic congenital conditions, including malformations. b. Genetic diseases have significant implications for breeders and the veterinarians who work with them. 5. Environmentally caused congenital malformations a. Teratogens are any exogenous agent that disrupts normal embryonic/fetal development. The result may be death, gross malformation or a milder structural or functional impairment. These factors might be chemicals, viruses, plants - even certain substances which are beneficial to the adult. i. For example: If a pregnant cow eats a certain type of lupine plant during days 40-70 of gestation, her calf is almost certain to be born with a defect called arthrogryposis (crooked calf disease). ii. For example: Vitamin A and its retinoid relatives must be present during early stages of development for normal organ formation, such as the heart, to occur. However, excess amounts of retinoids at certain stages will cause defective development in these same organs! If a little is good, a lot is NOT always better! b. The stage of development of the embryo/fetus at the time it encounters the teratogen is a major factor in determining its susceptibility. We often speak of the entire period of gestation as having three periods. Although there are exceptions to these generalizations, many teratogens affect the organism very differently, depending on which developmental period the organism is in at the time it encounters the teratogen. i. Pre-embryonic period – very early development, prior to gastrulation (described in Chapter 5); since there are so few cells, teratogens encountered at this time generally either cause death of the whole embryo, or have no effect. Specific defects that affect only a limited area (extra digits (polydactyly), for example) would not be caused at this stage, because specific regions of the embryo (digits) haven’t been formed yet. The effect is generally all (death) or none. ii. Embryonic period - organ formation occurs; teratogens encountered during this period interfere with organ formation and so result in many of the defects we will discuss. iii. Fetal period - growth and maturation; effects of teratogens may be more subtle. iv. Critical periods - specific times when particular organs are forming and therefore when those systems are most vulnerable to teratogens. 3 2024 Chapter 1 An example that starts with a case history and integrates core concepts of embryology and developmental biology that will be detailed in this course. The protein encoded by the Sonic Hedgehog gene is an example of a morphogen, which is a substance that differentially specifies cell fate, guiding growth and differentiation during embryogenesis. The Sonic Hedgehog signaling pathway regulates numerous aspects of embryogenesis including development of the brain, face, and limb. Exposure to compounds that inhibit the Sonic Hedgehog pathway cause birth defects; the specific clinical manifestation of which depends upon the timing of exposure. Postnatally, Hedgehog signaling is critical for maintenance of progenitor cells, and tissue healing and repair processes, and aberrant activation of the pathway is associated with malignant growth, including several types of cancer. The Sonic Hedgehog pathway is an excellent example of the importance of critical periods in development, gene-environment interactions in birth defects, and the relevance of developmental signaling pathways to postnatal health and disease. For those of you interested in learning more, these topics have recently been chronicled in easy-to-read papers. 1. Of embryos and tumors: Cyclopia and the relevance of mechanistic teratology, 2021 by DeSesso https://onlinelibrary.wiley.com/doi/10.1002/bdr2.1636 2. Gene-environment interactions: aligning birth defects research with complex etiology, 2020 by Beames and Lipinski https://journals.biologists.com/dev/article/147/21/dev191064/226367/Gene-environment- interactions-aligning-birth “Between fertilization and birth, the developing organism is known as an embryo. The concept of an embryo is a staggering one, and forming an embryo is the hardest thing you will ever do. To become an embryo, you had to build yourself from a single cell. You had to respire before you had lungs, digest before you had a gut, build bones when you were pulpy, and form orderly arrays of neurons before you knew how to think. One of the critical differences between you and a machine is that a machine is never required to function until after it is built. Every animal has to function as it builds itself.” Scott F. Gilbert Developmental Biology, 6th Ed. THOUGHT QUESTIONS: A client has called you to look at a severely malformed new-born calf. He wants to know what caused the problem and whether he must avoid breeding the same stock in the future. What general kinds of information would you need to answer this question? Are all congenital defects hereditary? 4