Chapter SummaryIn chapter 5 we saw that cells located superficially in the vertebrate embryo invaginate through the primitive streak and ultimately acquire a mesodermal fate. The mesodermal layer gives rise to most of the internal organs of the animal. Gastrulation organizes the different germ layers, and cells in each of the germ layers begin to acquire specific fates during gastrulation and after it is complete.
In an amphibian embryo, the cells lying closest to the Spemann organiser give rise to the dorsal mesodermal derivatives, that is, the notochord and the somites. These cells come to lie under the neuroectoderm and are subjected to signals emanating from the overlying neuroectodermal cells. The dorsal mesodermal cells are exposed to higher levels of BMP antagonists and are thus subjected to lower levels of active BMP signaling. Lateral regions are subjected to higher levels of BMP signaling, thus a gradient of BMP is established which is thought to be primarily responsible for spatial patterning of the mesoderm. Low levels of BMP signal give rise to dorsal mesoderm while still lower levels are responsible for the specification of lateral and ventral mesodermal tissue. Subsequent events that involve changes in cellular morphology and also cell migration lead to the congregation of the dorsal midline cells into the notochord, which is a transient rodlike structure.
Cells on either side of the developing spinal chord aggregate into blocks called somites. A characteristic feature of somitogenesis is a wave of periodic gene expression through the presomitic mesoderm. Genes such as hairy have been shown to be expressed in waves in a temporally regulated fashion. Expression of the hairy gene and those regulating its expression are thought to regulate the temporal periodicity of somite formation and thus segmentation. This process has been well studied in the chick embryo, where the idea of a segmentation clock has been established.
The somite may be grossly divided into two regions: the sclerotome and the dermamyotome. [fig 7.4] The sclerotome, which is the medio-ventral portion of the somite, gives rise to cartilage that is the actual precursor of the vertebral column. Cartilage arising from the sclerotome undergoes a process called endochondral ossification to ultimately give rise to bone. Bone formation is itself under the control of various signaling molecules, one of the important ones being Indian Hedgehog (Ihh).
The dorsal portion of the somite is called the dermamyotome and is further subdivided into the dermatome and the myotome. The dermatome develops into the dermis of the skin. This process is under the control of factors released from the overlying ectoderm and the dorsal neural tube. The myotome is the precursor of muscles. An important feature of striated muscle differentiation process is that its precursor cells, which are called myoblasts, often go into a prolonged resting phase. The activation of myoblasts by as yet unidentified signals results in them expressing muscle specific genes; the myoblasts fuse with each other, resulting in a syncytial muscle fiber.
It must be noted that the actual process of patterning the somite is under the influence of signals emanating from the notochord as well as the neural tube. Signals emanating from the dorsal and ventral regions of the neural tube have different consequences on somite patterning; the former ordinarily induces the differentiation of striated muscles whereas the latter induces the formation of cartilage. Some of the signaling molecules responsible for the aforementioned patterning processes have been identified, and the list includes molecules such as BMP, Wnt, and Shh. [fig 7.7]
The region of the mesoderm that is lateral to the somites and dorsal to the forming coelom is called the intermediate/lateral mesoderm. The lateral mesoderm is the precursor of kidneys, gonads, the somatopleure, and the splanchopleure. The most dorso-medial portion of the lateral mesoderm is often called the nephrotome, and it is the precursor of the tubules and ducts that make up the kidney. Kidney development is a highly complicated process. Briefly, kidney development in amniotes goes through three different stages; the precursor pronephros stage, the intermediate mesonephros stage, and the definitive metanephros stage. Elongation of a specialised tubule called the Wolffian duct and specification of the metanephric mesenchyme are the primary processes of metanephric kidney morphogenesis. This is followed by the formation of the ureteric diverticulum and branching of the ureteric bud, which ultimately leads to the formation of the renal vesicles. Final epithelial differentiation and tubulogeneis are accompanied by vascularization. Kidney morphogenesis also involves intercellular signaling molecules such as BMP4. [fig 7.12]
The mesoderm that is located ventromedially to each nephrotome is called the genital ridge, which is where the gonads differentiate. Sex cords are formed in this ridge followed by migration of Primordial Germ Cells (PGCs) into the area. Subsequent events associated with male or female gonad development are different. In a male embryo, sex cords proliferate and become seminiferous tubules; Sertoli cells differentiate in the tubules and secrete anti-Mullerian duct factor. PGCs then form the spermatozoa. The seminiferous tubules connect to the Wolffian duct, which becomes the vas deferens of the male reproductive system. In the female, a new set of sex cords develop after the first set degenerates. These ultimately form the prospective follicle cells that surround the oocytes. The Wolffian duct degenerates in the female while the Mullerian duct persists and ultimately becomes the oviduct. [fig 7.14]
Mesenchymal cells produce a reticular network in which the central cells differentiate into erythrocytes. Blood vessels are generated by the formation of endothelial tubes by a process called vasculogenesis. Some of the blood vessels may also be formed by invasion of preexisting endothelial tips into the surrounding tissue by a process called angiogenesis. Angiogenesis has been shown to be dependent on factors such as VEGF and angiopoietin. An important feature of erythropoeisis is that the principal sites of erythropoeisis change from one location to another, the types and proportions of cellular constituents of blood changes, and the molecular constitution of hemoglobin in erythrocytes also changes.
The splanchnic layer of the anterior ventral mesoderm forms an endothelial tube, connected to the rest of the developing vasculature. This develops a specialized muscle layer called the myocardium. Heart formation is a highly complicated process and occurs on both sides of the developing gut in amniotes. [fig 7.16] The bilateral heart primordia subsequently fuse to form a single tubular heart. Furthermore, the anatomy of the blood vessels undergoes extensive remodeling during the course of embryonic development.
Limb buds originate from the lateral somatic mesoderm. Positioning of the anterior and posterior limb buds is dependent on hox genes. As the limb bud grows, the Apical Ectodermal Ridge (AER) becomes prominent on the distal tip of the limb bud. It is now known that the AER is crucial for limb outgrowth, and this was made evident by experiments that involved the removal of the AER. The longer the ridge was allowed to be on the limb bud before its removal, the more distal were the final structures that developed. Earlier removal allowed only the upper-limb (proximal) structures to develop. In addition, the ectodermal covering overlying the limb bud provides signals to organize the dorso-ventral polarity of the limb. The anterior-posterior organization of the limb is regulated by the zone of polarizing activity (ZPA), a group of cells located in the mesenchyme in the posterior portion of the limb bud.
Molecules such as VegT and TGF? are responsible for the determination of endoderm. By the end of gastrulation, the endoderm lines the archenteron and forms a tube, which stretches from the anterior to the posterior ends of the embryo. Subsequent organogenesis and associated morphogenesis differentiate the endoderm into the digestive system and the related organs. Different regions of the endoderm give rise to different organs. For example, the pharyngeal region develops the thyroid and parathyroid glands in addition to the thymus. Lungs develop from the esophageal region of the gut, while the liver and pancreas form from the endoderm adjacent to the stomach and duodenum. It should be noted that a complex set of intercellular interactions is involved in the development of these organs.
Further ReadingA nice article on the evolution of mesoderm and endoderm.
U. Technau and C. B. Scholz. Origin and evolution of endoderm and mesoderm. International Journal of Developmental Biology 47 (2003): 531-39
The Stainier Lab at UCSF, among others, studies the formation and function of the vertebrate endoderm.
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