SEM_05_Organogenesis. Germ layers derivatives_PARTE1.docx

Organogenesis. Germ layers derivatives Learning objectives Understand how a flat structure, the embryonic disc, turns into a cylindrical body. Consider how embryonic cells assemble into the first embryonic tissues. Describe the early ectodermal derivatives. Describe the early mesodermal deri...

Organogenesis. Germ layers derivatives Learning objectives Understand how a flat structure, the embryonic disc, turns into a cylindrical body. Consider how embryonic cells assemble into the first embryonic tissues. Describe the early ectodermal derivatives. Describe the early mesodermal derivatives. Describe the early endodermal derivatives Organogenesis In animal development, organogenesis (etymologically “organ generation") is the process by which the three germ layers (the ectoderm, endoderm, and mesoderm) develop into all the specific tissues and organs that compound one organism. The first organogenesis period, or embryonic period, occurs during the first weeks of development (in humans, between the third and eighth weeks of gestation). By the end of this period (in humans, second month), the main organ systems have been established, rendering the major features of the external body. An organ or tissue in its earliest recognisable stage of development is referred to as a primordium (primordia in plural), the initial set of cells from which an organ can grow. Most of the organ primordia are established during the organogenesis what makes this stage the most sensitive period for inducing birth defects. Most major malformations are produced during the period of organogenesis (teratogenic period; third to eighth weeks in humans), but in stages before and after this time, the foetus is also susceptible, so that no period of gestation is completely free of risk. During this period, the notochord plays an important role, as a major inductor, in leading the early changes, such as inducing the formation of the neural plate, and ultimately the neural tube (neurulation). It coincides with the first evidence of the boundaries of an actual embryonic body which allows distinguishing the tissues that will form the embryonic organs from other tissues that remain outside of the embryo forming extra-embryonic organs. The term conceptus includes all the tissues and organs derived from the zygote: the embryo as well as its associated extra-embryonic membranes. Development of the first cylindrical body The early embryo is flat, but soon, by the end of the third week, the vertebrate body must be transformed into a cylindrical structure which encloses the first cylindrical organs (gut, neural tube, notochord, etc.) inside of it. The body formation takes place by folding the ectoderm around the notochord which remains in the middle as the central axis of the body. Basically, the following folds are responsible for the early formation of the body: The head fold or cranial fold. The cylindrical cephalic folding is the first to develop when the region of the embryonic disc located immediately cranial to the notochord bends ventrally. Consequently, the most cranial part of the embryo is the first to be formed. This fold pulls ventrally the cranial part of the embryonic disc, most likely due to the rapid growth of the forebrain and the relative stiffness of the notochord. This process brings the mouth and heart, initially located anterior to the notochord, into their ventral positions. The folding of the head also affects the endoderm which is also reflected ventrally upon itself, forming a blind-ended tube called foregut inside of the cephalic fold. The elongation also incorporates the most anterior part of the mesoderm (half-dozen somites) into the future head. The lateral body folds. While the cranial and caudal folds define the head and tail respectively, the lateral parts of the embryonic disc elongate and bend ventrally enclosing the underlying mesoderm and endoderm inside of the body. Insofar the body folds meet and fuse ventrally, the ventral aspect of the body that was wide open and the beginning is gradually closed. As a result, the endoderm trapped inside of the body also closes into a tube called midgut. The tail fold or caudal fold. At the caudal end of the embryo, a cylindrical tail process is formed in a manner similar to that of the head process. It also encloses part of the mesoderm and the endoderm which is also folded in a blind-ended tube called the hindgut. https://sway.office.com/u0iLxHnPhRK5Hl03#content=9gBswoiBOh7Ihp - Folding of the body in a longitudinal section https://sway.office.com/u0iLxHnPhRK5Hl03#content=Puc2par0gdwhOz - Folding of the body in a transversal section The delimitation of the embryonic body establishes a clear separation between the embryonic tissues (intraembryonic tissues) and the extra-embryonic tissues that extends beyond the embryo itself. Up to this stage, the ectoderm, mesoderm, and endoderm expand throughout the embryonic disc without any distinguishable boundary between the body of the embryo and its surrounding. As the cranial, lateral and ventral body walls are formed, the lateral mesoderm and the coelomic cavity are partly incorporated within the body (embryonic coelom) while another large part of the primitive coelom remains outside the body (extra-embryonic coelom); The same occurs with the endoderm, which is partly incorporated into the embryo to form the intestine (fore, middle and posterior intestine) while a large part remains outside the embryo (yolk sac). Gradually, as the body closes ventrally, the initial wide opening of the body gradually narrows to form the umbilicus or umbilical cord whereby the embryonic body remains open and communicates with the extra-embryonic structures (placenta) during gestation. This is the case of the endoderm whose broad initial connection of the intestine (intra-embryonic) with the yolk sac (extra-embryonic) is progressively reduced to a narrow yolk stem or yolk duct. In the umbilical cord, the amnion surrounds this tubular passage where vital structures (blood vessels, yolk sac, and allantois) enter and exit the embryo. Therefore, the function of the umbilical cord is to allow the transport of substances, nutrients, gases and wastes between the fetus and the extra-embryonic organs (placenta). https://sway.office.com/u0iLxHnPhRK5Hl03#content=eBMKmxdWYu0lvG - Distinction between intra-embryonic tissues and extra-embryonic tissues Early embryonic tissues Before delving into the germ layer derivatives, let’s consider how cells are primarily arranged to form the early embryonic tissues. In the early embryo, cells can be arranged forming two types of tissues: epithelium or mesenchyme Epithelium (epithelia in plural) is a sheet of cells that covers structures and lines organs, vessels (blood and lymph), and cavities. The cells in the epithelial tissue are very closely packed together and joined with little space between them (tight junctions). Mesenchyme is a kind of filling tissue or connective tissue found mostly during the development of the embryo. It is composed mainly of loose cells connected by gap junctions and embedded in a mesh of proteins and fluid, called the extracellular matrix. Mesenchyme gives rise to a variety of connective tissues throughout the body, such as bone, muscle and cartilage. The mesenchyme also develops into the tissues of the circulatory and lymphatic systems. https://sway.office.com/u0iLxHnPhRK5Hl03#content=J5vKfvlrXYTLcA - Epithelia versus mesenchyme in early embryonic tissue organisation While most of the ectodermal and endodermal cells are organised into epithelia, the mesoderm can exist in both morphologic forms, but this organisation is not irreversible. Mesoderm can transform from mesenchyme to epithelium and vice versa. Cells can change their characteristics from those of an epithelium, having strong intercellular connections, to become more loosely organised and, therefore, capable of migration. At gastrulation, epithelial cells from the epiblast turn into primary mesenchymal cells to streams through the primitive streak and then they will be transformed again into temporary epithelia such as the somites and the lateral mesoderm. Later, these temporary epithelia will transform once again into mesenchyme which ultimately forms muscle and connective tissue. Thus, the term “mesenchyme” refers to the morphologic appearance of an embryonic tissue regardless of the germ layer from which are originated. As a result, although most of the primary mesenchyme comes from the mesoderm, the ectoderm and endoderm, which are primarily epithelia, can also derive into mesenchyme. - Differentiation of blood vessels epithelia from mesenchymal tissue. The terms mesenchyme and epithelium are correlated with the type of tissue organisation and not to any specific germ layer. Besides, tissue organisation can change throughout development so that mesenchyme can be reorganised into new epithelia as it happens with blood vessel development. Ectodermal derivatives The ectoderm is responsible for the formation of many organs inside and outside the embryo. In the embryo the first, and most outstanding, ectodermal derivative is the nervous system, which is formed by a process that is called neurulation. Outside the embryo, the ectoderm gives rise to the amnion. https://sway.office.com/u0iLxHnPhRK5Hl03#content=vr76Firgw0OUwq - Ectodermal derivatives Although ectoderm can be easily correlated with the origin of the skin epidermis, the nervous system and the amnion are two outstanding structures derived from the ectoderm. Neurulation Neurulation is the formation of the neural tube from the embryonic ectoderm. This process starts after gastrulation with a first stage called primary neurulation. The notochord sends signals to the overlying ectoderm, inducing it to become neuroectoderm. The result is a strip of neuronal stem cells that runs along the back of the foetus. This strip of thickened ectoderm in the midline, called neural plate, will be the origin of the entire nervous system. First, the neural plate folds ventrally to form the neural groove. Then, the neural groove deepens and its dorsal edges fuse in the midline to form the neural tube. https://sway.office.com/u0iLxHnPhRK5Hl03#content=hOqMRqufZsUOlZ - Primary neurulation The primordium of the nervous system is defined by the formation of the neural tube. The neural tube starts to close from the centre of the developing foetus and progresses cranially and caudally. This leads to two temporal openings located in the anterior (rostral neuropore) and posterior (caudal neuropore) ends of the neural tube. The rostral neuropore closes midway through the embryonic stage with the closure of the caudal neuropore shortly afterwards. In humans, the anterior neuropore closes on or before the 26th day of development, and the caudal neuropore closes before the end of the fourth week. Failure in the closure of the cranial or caudal neuropore results in two well-known congenital conditions called anencephaly and spina bifida, respectively. https://sway.office.com/u0iLxHnPhRK5Hl03#content=xqA3YP2ukpU3Ze - Anencephaly Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs when the cranial neuropore fails to close. https://sway.office.com/u0iLxHnPhRK5Hl03#content=2uplgR1RzKsdT9 - Spina bifida Spina bifida is a birth defect in which there is incomplete closing of the caudal neuropore and, as a result, the spinal cord and the surrounding membranes remain open. In the secondary neurulation, after the closure of the neural tube, it loses its connection with the surface ectoderm, which will become the future epidermis of the skin. The development of the vertebrae leads to the formation of the vertebral canal that ultimately encloses the part of the neural tube that will become the spinal cord. Bilaterally, as the neural groove closes, cells detach from where the neural groove was joined to surface ectoderm. These cells proliferate and assume a position dorsolateral to the neural tube, forming the neural crests. Whereas the neural tube becomes the central nervous system (the brain and spinal cord) the neural crest cells are remarkable for the range of structures they will give rise. Besides forming the peripheral nervous system, the neural crest cells migrate widely and participate in the formation of many structures, such as the pigment cells in the skin (melanocytes) and large parts of the craniofacial mesenchymal derivatives. https://sway.office.com/u0iLxHnPhRK5Hl03#content=PdDTgxMlh4wgZj - Neural crests and spinal cord In the body trunk, the neural tube differentiates into the spinal cord. Other nervous structures such as the spinal ganglia and the peripheral nervous system are contributed by the neural crests. The development of the brain takes place when bulge-like expansions, called brain vesicles, grow from the cranial end of the neural tube. The three primary brain vesicles (rhombencephalon ; metencephalon or midbrain; prosencephalon or forebrain) differentiate into five secondary brain vesicles (rhombencephalon -> myelencephalon and metancephalon; metencephalon or midbrain; prosencephalon or forebrain -> diencephalon and telencephalon), which eventually develops into all the functional adult brain structures. https://sway.office.com/u0iLxHnPhRK5Hl03#content=lI5x0k92dHG74T - Development of the brain vesicles The development of the brain is associated with a set of dilations that appear in the cranial region of the neural tube. They are referred to as the brain vesicles. Amniogenesis While the body is folding, and neurulation is taking place, an extra-embryonic membrane, the amnion, is formed from the extra-embryonic ectoderm. Besides the ectoderm, the adjacent parietal (somatic) mesoderm also contributes to the amnion formation, so that the amniotic wall is made of a bi-layered membrane: ectoderm that faces the amniotic cavity and squamous parietal mesoderm that lies below. The amnion is a membranous sac that surrounds and protects the embryo. It develops in reptiles, birds, and mammals, which are hence called amniotes. Ancestors of reptiles, birds and mammals shifted from an aquatic (fish) or semi-aquatic (amphibian) lifestyle to a fully terrestrial one. For this to be successful, the embryos of amniotes were provided with their own aquatic environment, which led to less dependence on water for development and thus allowed the amniotes to proliferate in drier environments. The amniotic cavity contains a fluid, the amniotic fluid, which bathes the outside of the embryo and cushions the embryo from bumps and injury. In most mammalian species, reptiles and birds, the amnion is formed by ectodermic folds that rise up over the embryo (amniogenesis by folding). In humans, on the other hand, the amnion develops earlier, before gastrulation, and in a more direct manner (amniogenesis by cavitation). Amniogenesis by folding. In reptiles, birds, and many mammals the amniotic folds (also called chorionamniotic folds) are a reflection of the ectoderm at the edge of the embryonic disc, where the extra-embryonic ectoderm meets the trophoblast (chorion). While the amniotic folds rise up and surround the embryo, the periphery of the embryonic disc falls ventrally. The amniotic folds are initiated in the cephalic region and then extend along the sides and the caudal end of the embryo. They gradually rise more and more up until its different parts meet and fuse over the dorsal aspect of the embryo, that is now enclosed inside of the amniotic cavity. This space is filled with a liquid, amniotic fluid, that is produced by the amniotic cells. This provides a protective environment for the embryo to safely develop throughout gestation. https://sway.office.com/u0iLxHnPhRK5Hl03#content=OXXOVYswyR0D7v - Amniogenesis by folding represented in a longitudinal section. After the edges of the amniotic folds fuse, the two layers of the folds become two separated membranes: the inner forming the amnion, the outer the chorion or serosa that will be described in the next chapter. At the point where the folds merge, a scar-like thickening, termed amniotic raphe or mesoamnion, is formed. In horses, dogs and cats, the amniotic raphe degenerates and the two layers of the amniotic folds become completely separated so that the amnion and the chorion become independent. Contrary, in ruminants and pigs the amniotic raphe persists throughout gestation permanently attaching the amnion to the chorion. When complete separation of the amnion occurs, as in the case of horses, dogs and cats, the foetus is often born covered with the amnion, which can be suffocating if not removed by the mother or an attendant. If the amniotic raphe persists throughout gestation, as it does in ruminants and pigs, most of the amniotic membrane remains attached to the placenta; hence, the foetus is generally born without being covered by the amnion. https://sway.office.com/u0iLxHnPhRK5Hl03#content=u31c3SMpAdVHVd - Development of the amnion in a transversal section https://sway.office.com/u0iLxHnPhRK5Hl03#content=FjpbqJAglJHpMr - Species-specific variations in the amnion layout inside of the embryonic sac. Amniogenesis by cavitation. In human embryos, amniogenesis takes place in earlier stages than in domestic mammals. In humans, the amnion is formed before gastrulation in a more direct manner. The amnion appears as a cleft in the inner cell mass of the blastocyst that grows to form the amniotic cavity. This primordial cavity is a sort of shortcut in development which accomplishes the same result as folding. The more superficial cells of the inner cell mass are situated next to the chorion and correspond to the amniotic membrane whereas the inner cells turn into the bilaminar embryonic disc (epiblast and hypoblast). - Amniogenesis by cavitation Mesoderm derivatives When the cylindrical body is formed the axial, paraxial and part of the lateral mesoderm are included inside of the body. Besides, the lateral mesoderm stretches out of the body boundaries; as a result, the primitive coelom is divided into the intraembryonic and extraembryonic compartments that communicate through the umbilical cord. https://sway.office.com/u0iLxHnPhRK5Hl03#content=P63QKTn8C52bTU - Mesoderm derivatives Whereas the axial, paraxial and intermediate mesoderm are located inside of the embryonic body, the lateral mesoderm expands widely outside of the body so that it can be described in two different areas: the intra-embryonic lateral mesoderm and the extra-embryonic lateral mesoderm. Axial mesoderm. Notochord The notochord is a rod-shaped aggregate of cells located in the midline between the ectoderm and the endoderm. It develops from the last migration of epiblastic cells through the primitive node; These last migrating cells are collected in the midline where they become the notochord. The notochord is important because it is a major inductor structure during the early organogenesis. Among others, it induces the formation of the body folds, the development of the nervous system, the formation of somites and the development of the intestinal tube. Nevertheless, the notochord is an embryonic transient structure that eventually will be replaced by the vertebral column. Although most of the notochord becomes ossified inside the vertebral bodies, some remnants persist in the centre of the intervertebral discs in a structure called the nucleus pulposus. https://sway.office.com/u0iLxHnPhRK5Hl03#content=3PoXxzruvQA7s2 - The axial mesoderm: notochord Paraxial mesoderm. Somites Somites are paired blocks of paraxial mesoderm arranged along the head-to-tail axis that develope in the early embryo. Somites are formed by bilateral segmentation of the paraxial mesoderm located on either side of the neural tube. The somites appear on both sides of the neural tube simultaneously. This segmentation does not occur in the head, rostral to the notochord, where the mesoderm forms the unsegmented cranial paraxial mesoderm. The pairs of somites differentiate gradually one after another, down the length of the embryo from the head to the tail, with each new pair of somites forming on the caudal side of those already existing. The process is sequential and therefore can be used as an indicator of the age of embryos based upon the number of pairs of somites visible at one specific moment during neurulation. The total number of somites formed is species-specific but broadly coincides with the number of vertebrae in each species. This is because somites are responsible for the metameric organisation (segmental organisation) of the embryo. Metamerism refers to the primitive segmental partitioning of the body in metameres (segments), which will persist in many definitive structures such as the spinal nerves, vertebral column, ribs and deep muscles. https://sway.office.com/u0iLxHnPhRK5Hl03#content=qjyYC8hNLX7SUY - The paraxial mesoderm: Somites Nevertheless, somites are embryonic transient structures that eventually derive into three different cell populations: The sclerotomes appear around the notochord as a result of migrations from both bilateral somites towards the midline. These migrating cells condense in the midline around the notochord to give rise to a new block, the sclerotome, for each pair of somites. The sclerotomes are the precursor of the axial skeleton which will mainly turn into the vertebrae and ribs. After the cells of the sclerotomes have left the somites, they adopt a flat shape. Then they are called dermomyotomes which can be divided into the myotome and the dermatome components. - Sclerotomes The myotomes are the precursor the muscular cells which lead to the formation of skeletal muscles. The short and deep muscles usually derive from individual myotomes and therefore they maintain their original metameric pattern. The broad and superficial muscles derive from the fusion of several myotomes but they always maintain their innervation from each of the original segments. From a clinical point of view, the term "myotome" refers to the group of muscles that develop in each metamere and are therefore innervated by the same spinal nerve. - Myotomes The dermatomes are the dorsal portion of the somites which gives rise to the connective tissues of the back skin (dorsal dermis); dermis of the ventral and flank regions is derived from parietal mesoderm. In each of the metameres, the dermatomes emigrate lateroventrally under the ectoderm. This migration drags the cutaneous branches of the nerves and vessels that maintain the original metameric pattern even when the dermis is eventually integrated into the skin as a continuous layer. From a clinical point of view, dermatomes refer to the areas of skin as bands that are innervated by each spinal nerve. - Dermatomes Intermediate mesoderm. Urogenital mesoderm It is a portion of mesoderm that is located between the paraxial mesoderm and the lateral plate mesoderm. It develops into the part of the urogenital system (kidneys and gonads), as well as the reproductive system. Lateral plate mesoderm. Coelom On either side of the intermediate mesoderm resides the lateral plate mesoderm. Each plate splits horizontally into: a lateral sheet, parietal mesoderm (also known as somatic mesoderm), which underlies the ectoderm and trophoblast. a medial sheet, visceral mesoderm (also known as splanchnic mesoderm), which overlies the endoderm. The parietal mesoderm contributes to the formation of organs originated from the ectoderm and the trophoblast, such as the body wall (ectoderm + parietal mesoderm) and some foetal membranes: chorion (trophoblast + parietal mesoderm) and amnion (ectoderm + parietal mesoderm). The visceral mesoderm contributes to the formation of organs originated from the endoderm, such as the gut (endoderm + visceral mesoderm) and some foetal membranes: yolk sac and allantois (endoderm + visceral mesoderm). The space between the parietal and visceral mesoderm becomes a cavity known as the coelom (also spelt as coelome), which stretches from the future neck region to the posterior part of the body. When the primal embryonic body is folded, and the umbilical cord is formed, part of the coelomic cavity remains inside the embryo (embryonic coelom) whereas the rest expands outside (extra- embryonic coelom). As development goes on, the embryonic coelom gives rise to the cavities of the body which will be divided into the pleural, pericardial, and peritoneal cavities, for housing the lungs, heart, and abdominal organs, respectively. https://sway.office.com/u0iLxHnPhRK5Hl03#content=NQqb9DvuRcqNMh - The lateral mesoderm The two layers of the lateral mesoderm enclose the primordial cavity of the body: the coelom.