What Does the Science of Embryology Have to Say About Unborn Babies
Embryology
Embryology is the basis for understanding the intimate relation between structures in different organ systems, such as the nervous system and musculus, and is primordial for understanding disorders of evolution that in the human may nowadays as one of the congenital myopathies.
From: Fetal and Neonatal Physiology (Fifth Edition) , 2017
Embryology, Beefcake, Histology, and Developmental Anomalies of the Liver
Mark Feldman Physician , in Sleisenger and Fordtran's Gastrointestinal and Liver Disease , 2021
Embryology
The liver develops at 3 to iv weeks' gestation equally an outgrowing diverticulum of proliferating endodermal cells from the ventral wall of the foregut in response to signals from the adjacent developing centre (Fig. 71.one). 1,2 In the quaternary week, 2 buds can be recognized in the hepatic diverticulum: the cranial bud becomes the liver and the hilar biliary tract, whereas the caudal bud develops into a superior bud that forms the gallbladder and cystic duct and an junior bud that forms the ventral pancreas. 3,4
Initially, the liver bud is separated from the mesenchyme of the septum transversum by basement membrane. one Soon, all the same, this basement membrane is lost, Eastward-cadherin expression is downwardly-regulated in hepatic cells, and cells delaminate from the bud and invade the septum transversum as cords of hepatoblasts—bipotential cells that differentiate into hepatocytes and cholangiocytes. 2,5,half-dozen As they invade the septum transversum mesenchyme, hepatoblasts intermingle with endothelial cells, an interaction that appears disquisitional for hepatic morphogenesis. 1
Hepatic differentiation is highly dependent on signals from the cardiogenic mesoderm and septum transversum mesenchyme, which produce fibroblast growth factor (FGF) and bone morphogenetic protein, respectively. 2,5 The control of hepatocytic differentiation is complex and involves several transcription factors at diverse stages of evolution. For example, GATA4 and forkhead box A (FoxA) are involved in developmental "competence" considering they take the ability to interact with compacted chromatin and act as "pioneer" factors that can mark domains of chromatin equally competent to be expressed in response to afterwards developmental cues such equally FGF 6,7 Prospero homeobox protein 1 (Prox1) may be involved in downwardly-regulation of E-cadherin, considering mutant hepatoblasts maintain loftier levels of Eastward-cadherin and fail to degrade the matrix surrounding the liver bud. half-dozen Last differentiation of hepatocytes requires the overlapping interaction of a group of transcription factors including hepatocyte nuclear factor (HNF)1β, FoxA2, HNF1α, HNF4α1, HNF6, and liver receptor homolog (LRH)-1. 6,7 These cross-regulating factors form a dynamic transcriptional network past binding to each other's promoters and to the promoters of other hepatic transcription factors, creating synergistic interdependence as hepatocyte maturation proceeds. seven The contribution of Wnt signaling and β-catenin is complex and stage dependent. During early development, approved Wnt/β-catenin signaling represses hematopoietically-expressed homeobox (Hhex), another early transcription factor in hepatic development; therefore, early in the process, Wnt must exist suppressed in the inductive endoderm to facilitate delivery of the endoderm to a hepatic fate. Afterward specification, Wnt signaling promotes hepatogenesis. 6,viii
Ontogenesis of Striated Muscle
Harvey B. Sarnat , in Fetal and Neonatal Physiology (5th Edition), 2017
Historical Groundwork
Embryology is the basis for agreement the intimate relation betwixt structures in unlike organ systems, such as the nervous system and musculus, and is primordial for agreement disorders of evolution that in the homo may present as ane of the congenital myopathies. The timing and sequence of striated muscle maturation are as precise and predictable as in the nervous organisation. Interest in neuromuscular ontogeny began with the studies of MacCallum 1 in the late nineteenth century. The account of histologic changes in developing human muscle published in 1917 by Tello ii in Spain remains every bit accurate and valid today as whatsoever subsequent studies by calorie-free microscopy. Ultrastructural studies of developing muscle past transmission electron microscopy began in the 1950s and were supplemented by studies using the scanning electron microscope two decades later. Histochemical techniques to demonstrate biochemical constituents and enzymatic activities in developing muscle were introduced in the 1960s and 1970s; the 1980s was a decade for the introduction of immunocytochemistry to identify other molecules of subcellular components. The late 1980s and early 1990s saw a major quantum in the agreement of musculus differentiation past the discovery of myogenic regulatory genes and their transcription products. Studies of the complex interactions of these genes, their translated proteins, and the part of various trophic factors go on to be the focus of current investigations in muscle ontogeny. Modern embryology, an integration of archetype descriptive morphogenesis and the molecular genetic regulation of myogenesis, is the foundation for understanding the pathogenesis of built myopathies. three
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Anatomy, Histology, Embryology, Developmental Anomalies, and Pediatric Disorders of the Biliary Tract
Mark Feldman Doctor , in Sleisenger and Fordtran's Gastrointestinal and Liver Disease , 2021
Embryology of the Liver and Biliary Tract
The human being liver is formed from ii primordia (Fig. 62.1): the liver diverticulum and the septum transversum (run into alsoChapter 71). i,2 Proximity of cardiac mesoderm, which expresses fibroblast growth factors (FGFs) 1, ii, and 8, and bone morphogenetic proteins cause the foregut endoderm to develop into the liver. The liver diverticulum forms through the proliferation of endodermal cells at the cranioventral junction of the yolk sac with the foregut and grows into the septum transversum in a cranioventral direction. Surrounding mesoderm and ectoderm participate in the hepatic specification of the endoderm to hepatoblasts, via signaling from mesodermal tissues, including ligands of bone morphogenic protein, Wnt, and FGF families of proteins. 1 After their specification and migration into the septum transversum, hepatoblasts undergo proliferation and migration between 26 and 32 days of gestation in the procedure of forming an organ bud. 1,3 The homeodomain transcription factors hematopoietically expressed homeobox (Hhex) and Prospero homeobox protein i (Prox1), in the anterior endoderm and hepatic diverticulum, are required for the migration of hepatoblasts into the septum transversum that precedes liver growth and morphogenesis. four,v Some other homeodomain protein, Hlx, is necessary for hepatoblast proliferation. At the v-mm stage, a solid cranial portion (hepatic) and a hollow caudal portion of the diverticulum can be clearly distinguished. The large hepatic portion differentiates into proliferating cords of hepatocytes and the intrahepatic bile ducts. Hepatocyte nuclear factor (HNF)4α expression drives further hepatocyte differentiation and epithelial transformation into the characteristic sinusoidal architecture. vi
Bipotential hepatoblasts express blastoff fetoprotein and markers for hepatocytes such as albumin and for keratin and cholangiocytes (cytokeratin 19, CK19). The transcription cistron sex-determining region Y-box 9 (SOX9) is the earliest specific biliary marker detected in endodermal cells that line the hepatic diverticulum. Its expression disappears as soon every bit hepatoblasts invade the septum transversum simply reappears in cells of the biliary lineage throughout the development. 1 This early alter occurs on the eighteenth day of gestation and corresponds to the two.5-mm stage of the embryo. The homeobox geneHhex is essential for proper hepatoblast differentiation and bile duct morphogenesis. 5 Members of the transforming growth factor (TGF)-β, Wnt, FGF, Hippo, GATA, FOXA, ONECUT2, and HNF3/forkhead transcription factor families and HNF6 are also required for formation and differentiation of gut endoderm tissues. three,4 The septum transversum consists of mesenchymal cells and a capillary plexus formed by the branches of the 2 vitelline veins. At the 3- to 4-mm phase, between the third and fourth weeks of gestation, the growing diverticulum projects equally an epithelial plug into the septum transversum.
Neuroembryology
G.P. Singh , in Essentials of Neuroanesthesia, 2017
Abstruse
Embryology is a branch of science that is related to the formation, growth, and development of embryo. It deals with the prenatal stage of evolution beginning from formation of gametes, fertilization, formation of zygote, evolution of embryo and fetus to the birth of a new individual. Two basic processes involved are growth and differentiation. These lead to germination of various tissues and organs in body specialized to perform specific functions. Neuroembryology is related to the development of central nervous organisation (brain and spinal cord) and peripheral nervous system (spinal, cranial, and autonomic fretfulness) in the body. These tissues develop from neural tube and neural crest cells. In this chapter we have described the origin and diverse stages of development of a multicellular, highly circuitous, and specialized nervous system from a single-celled zygote.
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Embryology of the Kidney
Alan S.L. Yu MB, BChir , in Brenner and Rector's The Kidney , 2020
Neural Development
Renal vascular tone and urinary functions are regulated by a dense neural network in the kidney that relays bidirectional signals to the encephalon. 521 Glomerular filtration charge per unit, renal blood catamenia, tubular resorption of fluid, electrolytes, and urinary solutes, likewise as the secretion of renin, are regulated by sympathetic innervations of the glomeruli, renal tubules and blood vessels. 522 Over the past decade, the renal sympathetic innervation has attracted considerable attention after information technology has been recognized that persistently elevated renal sympathetic nerve activity contributes to the pathogenesis of renal hypertension. 523,524 In detail, it has been shown that surgical excision of sympathetic input to the kidneys tin alleviate refractory hypertension. 525,526 The distribution of afferent and efferent nerves to the kidney has been partially mapped but the developmental program involved in establishing them is largely unknown. 527–529 Fate mapping and molecular studies specifically addressing the origin and evolution of renal nerves take still to be reported, although many lessons have been learned about guidance pathways in play in both neural and vascular development in other systems. Neurons, like early blood vessels, appear to closely track the branching UB in cultured embryonic kidneys. 33,370,530 It can be speculated that the sympathetic innervation and vascularization of the kidney are coordinately synchronized with improve known anterior events between the UB and the MM.
Neoplasia
Thomas C. King MD, PhD , in Elsevier'due south Integrated Pathology, 2007
Hematopoietic Neoplasms
Normal hematopoietic cells express cell surface receptors that let them to drift from place to identify using the vasculature equally a conduit with specialized receptors that recognize endothelial cells in specialized lymphoid organs. Many hematopoietic neoplasms traffic extensively through the vascular or lymphatic systems (or both), since they retain these specialized receptors (run across Fig. 5-23F). Hematopoietic cells as well have cytoskeletons that permit them to undergo diapedesis and transmigrate endothelial surfaces into tissue. Considering of these intrinsic properties, the spread of virtually hematopoietic neoplasms through the body is non referred to as metastasis, and many hematopoietic neoplasms (east.1000., leukemia) are widely disseminated at the time of diagnosis. In contrast, most carcinomas and sarcomas must acquire new abilities before they tin metastasize.
Neural Crest
Neural crest cells are sometimes chosen the fourth germ jail cell layer and derive from a grouping of specialized cells that reside adjacent to the crest of the neural ridge during neurulation. Neural crest cells and then migrate extensively into the cranium, trunk, vagal and sacral regions, and center. Their migration is associated with downwardly-regulation of N-cadherin expression.
Differentiation of neural crest cells is largely controlled by environmental stimuli, including paracrine signaling:
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BMP2 (bone morphogenetic protein) → cholinergic neurons
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Glial growth factor → Schwann cells
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Endothelin-3 → melanocytes and adrenergic neurons
Neural crest cells besides give rise to a wide variety of other mature cell types including neurons in the peripheral nervous system, melanocytes in the skin, epinephrine-producing cells in the adrenal medulla, and connective tissue cells in the head and neck. Many neural crest prison cell derivatives retain some differentiated features typical of neuroendocrine cells.
Other characteristics of hematopoietic neoplasms differentiate tumorigenesis in these cells from tumorigenesis in epithelial cells. Leukemias tend to develop from committed stem cells or progenitor cells that have substantial replicative capacity. Because of this, disruption of fewer cellular pathways may be required for tumorigenesis in hematopoietic cells. Many leukemias, lymphomas, sarcomas, and pediatric neoplasms develop as a consequence of specific translocation events that form chimeric proteins with novel functions (see in a higher place). These specific translocations are now used to diagnose and classify many of these neoplasms. In some circumstances, myelodysplasia (similar to epithelial dysplasia) tin develop in hematopoietic lineages with the stepwise accumulation of genetic abnormalities. Leukemias that arise in the setting of myelodysplasia are usually phenotypically and clinically distinct from those resulting from specific chromosomal translocations and typically are refractory to treatment.
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Developmental Disabilities and Metabolic Disorders
Mary Lee Gregory , ... Bruce K. Shapiro , in Neurobiology of Brain Disorders, 2015
Embryonic Development
Embryology is a vast field, which would require its ain textbook to cover in even minimal detail. For the purposes of this chapter, the reader should understand that the maturational process from fertilized egg to term infant is ordered, proceeding according to a gear up schedule ( Fig. 3.one). The organism is offset one jail cell (the zygote), which then divides, and this process is repeated over and over again. Initially these cells are undifferentiated; they take the potential to class any function of the developing body (i.eastward. pluripotent stem cells). However, over time, cells go progressively more differentiated. They acquire item characteristics of the mature cell type that they will become and lose the potential to form other types of cells. As these initial pluripotent stem cells are differentiating into more specialized cells, the organism that is being formed past these cells is also progressively differentiating. The growing mass of cells develops an axis and gradually begins to course the major structures and organ systems of the human being body.
Effigy 3.ane. Embryological evolution and periods of susceptibility.
Source: Reprinted from Moore and Persaud. Before Nosotros Are Born: Essentials of Embryology and Birth Defects. Saunders/Elsevier; 2008, 1 with permission.Read full affiliate
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Genetic and Perinatal Affliction
Thomas C. Rex Doc, PhD , in Elsevier's Integrated Pathology, 2007
Down Syndrome
Downwards syndrome occurs in 1 in 1000 live births and results from the presence of iii copies of chromosome 21 (trisomy 21), which is one of the smallest autosomes. The likelihood of producing a baby with Down syndrome increases steeply with maternal age over 35 years. Affected individuals have some degree of mental retardation, which may be relatively mild or severe. Patients with Down syndrome also have an increased frequency of other built abnormalities such every bit congenital heart affliction (tetralogy of Fallot is the most mutual; see Chapter vii). Many phenotypic consequences of Down's syndrome announced to exist related to gene dosage. Down syndrome patients are at significantly increased chance for myeloid leukemia, which is thought to exist related to the additional copy of the bcr gene on chromosome 21 (the bcr factor is the translocation partner of the abl proto-oncogene in most cases of chronic myeloid leukemia). Gene dosage also results in the onset of Alzheimer's disease at an early age because of the inheritance of three copies of the amyloid forerunner protein gene on chromosome 21 (encounter Chapter fourteen).
Oligohydramnios
Amniotic fluid is essential for normal fetal growth and development and provides a cushion from concrete trauma. Amniotic fluid is required for the formation of pulmonary alveoli, and fetal animate of amniotic fluid is an essential physiologic stimulus for this process. Oligohydramnios is defined every bit an amniotic fluid index of less than five cm by ultrasound and affects approximately 4% of pregnancies in the United states of america.
Membrane rupture is the most common crusade of oligohydramnios late in pregnancy, and it can lead to cord compression and fetal distress. Oligohydramnios tin also be acquired by maternal apply of angiotensin-converting enzyme (ACE) inhibitors or prostaglandin synthase inhibitors.
The most common causes of oligohydramnios early in pregnancy are bilateral renal agenesis (Potter'due south syndrome), autosomal recessive polycystic kidney disease, and various forms of obstructive uropathy that forbid the passage of urine to replenish inspired and swallowed amniotic fluid.
Deficient amniotic fluid during pregnancy results in characteristic abnormalities of the external features (including hypertelorism, low-set ears, micrognathia, bowed legs, and narrow chest) that result from fetal compression in utero.
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Nervous System
Thomas C. King Md, PhD , in Elsevier'southward Integrated Pathology, 2007
CEREBRAL EDEMA AND HERNIATION
Cerebral edema develops in response to any encephalon injury, infection, or tumor but also can be idiopathic or related to environmental factors (e.one thousand., high altitude or drug exposure).
Embryology of the Central Nervous Organisation
Early sectionalization of the neural tube forms the major divisions of the CNS including the telencephalon (cerebral hemispheres), diencephalon (thalamus and hypothalamus), mesencephalon (midbrain), metencephalon (pons and cerebellum), and myelencephalon (medulla). Following this segmentation, there is extensive proliferation and migration of neurons between 8 and xvi weeks' gestation. Abnormalities of neuronal proliferation (microcephaly) or migration at these stages consequence in severe developmental abnormalities.
Later 16 weeks' gestation, neural proliferation diminishes just neural migration continues with prominent synapse formation and proliferation of glial cells that begin to myelinate axons. Many aspects of CNS evolution, specially neuronal migration and polarity, are controlled by paired homeobox genes. Genes (such as Notch) make up one's mind cell lineage. Cell partitioning is regulated predominantly by protein kinases.
Neuronal differentiation is orchestrated by neuronal precursor selector genes (of the helix-loop-helix family). Programmed neuronal death (apoptosis) is also disquisitional for normal CNS evolution.
Claret-Brain Barrier
The blood-brain bulwark was discovered in the 19th century by Paul Ehrlich, who injected aniline dyes into the vasculature of animals and observed that dye did not penetrate the CNS as information technology did other tissues. The blood-brain bulwark allows the same signaling molecules (e.k., hormones, cytokines) to be utilized in the CNS and peripheral tissues without cantankerous-talk betwixt the two systems. Blood vessels in the hypothalamus lack a blood-encephalon barrier then that hypothalamic neurons can respond to hormone levels in the apportionment (e.1000., leptin).
Structurally, the blood-brain barrier is formed by tightly packed endothelial cells forth all blood vessels in the CNS. This arrangement prevents move of molecules between endothelial cells. Capillary networks outside the CNS let variable amounts of solute flow between endothelial cells. The fenestrated endothelium of renal glomeruli allows the most extensive periendothelial solute flow in normal physiology.
The blood-brain barrier effectively blocks movement of molecules into the CNS unless they are lipid soluble or use specific transporters on endothelial cells. Enzyme systems in endothelial cells inactivate some lipid soluble compounds (e.g., L-dopa) to prevent their entry into the CNS.
Monoclonal antibodies reactive with by α4βi-integrin (a treatment for multiple sclerosis that blocks T-jail cell access to the CNS) tin can directly damage the blood-brain barrier, which expresses this adhesion molecule.
Since the cranial vault is a closed infinite, increased brain volume tin displace portions of the brain stem into the foramen magnum and event in herniation. As herniation progresses, the cerebral vasculature is compressed, causing ischemia and hemorrhage that is rapidly fatal. Cognitive edema tin be decreased by treatment with corticosteroids and by lowering blood CO2 levels to induce cerebral vasoconstriction and decrease the constructive claret book in the brain. Localized cognitive edema around tumor or infarcts can crusade midline shift and may upshot in additional neurologic abnormalities (Fig. 14-iii).
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Future Directions: Assisted Reproductive Technologies equally Tools for Creating Nonhuman Primate Models of Developmental Disability
Eric S. Hayes , ... Jennifer C. Potter , in Primate Models of Children'south Health and Developmental Disabilities, 2008
BRIEF HISTORY AND Status OF NONHUMAN PRIMATE ARTS
Embryology and stem cell-based ARTs in nonprimate mammalian species long predated ( Meissner and Jaenisch, 2006) the birth of Louise Dark-brown in 1978 (Steptoe and Edwards, 1978), the first human infant produced by in vitro fertilization (IVF) (Effigy 15.i). In 1984, 6 years after Louise Chocolate-brown, the kickoff nonhuman primate derived from IVF-produced embryos was built-in (Bavister et al., 1984). Since 1984 the progress of nonhuman primate ARTs has followed progress of man ARTs related to embryo product, in vitro culture, and cryopreservation. Live-born nonhuman primates were produced from frozen–thawed embryos and the utilize of intracytoplasmic sperm injection (ICSI), a technique whereby sperm are injected directly into mature oocytes using a fine glass pipette, in 1988 and 1998, respectively 4 and 6 years after successful conduct of the aforementioned procedures in humans (Figure fifteen.1).
FIGURE 15.1. A brief history of nonhuman primate (NHP) assisted reproductive technologies (ARTs) including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), embryonic stalk jail cell (ESC) development, nuclear transfer (NT), and transgenesis. "Fresh" indicates the utilise of fresh embryos. "Frozen" indicates the use of frozen/thawed embryos. Selected mouse and human ARTs are included for comparative purposes. Numbers in parentheses indicate the relative guild of Art occurrence over fourth dimension.
There are, nonetheless, two notable exceptions. Showtime, in 1995–1996 embryonic stalk cells were derived from blastocyst phase embryos of two species of nonhuman primate (Thomson et al., 1995, 1996), 1 of which is an One-time World species of monkey sharing greater than 95% genetic identity with humans. Human being embryonic stem cells were derived by the same group using similar techniques, merely not until 1998 (Thomson et al., 1998). Second, in 1997, live born nonhuman primate offspring were produced using nuclear transfer (NT), a technique that involves injection of a diploid jail cell into an oocyte that has had the genetic textile removed (Meng et al., 1997). The oocyte is believed to reprogram the nucleus of the injected jail cell back to its embryonic country. Where successful reprogramming has occurred, the donated cell so acts as a full diploid content of Dna, replacing DNA that would ordinarily exist provided past sperm and oocyte. This technique serves as the basis of beast cloning (Wilmut et al., 1997). This technique can also exist used to produce transgenic animals in situations where a genetic modification tin be made to the donor cell and maintained throughout subsequent development following nuclear transfer (Landry et al., 2005).
Ethical and legal considerations dictate that NT procedures will non be practical to humans in the about future, if at all. Therefore, although advances in human being ARTs continue to serve every bit the model for basic gamete biology and embryology that support nonhuman primate ARTs (e.g. ovarian stimulation, embryo culture and embryo cryopreservation) awarding of advanced ARTs in nonhuman primates is now poised to parallel advances in other domestic species and rodents. To this end a transgenic nonhuman primate was produced in 2001 using virus-mediated factor transfer (Chan et al., 2001) and several groups are at present actively involved in developing methods that aim to support nonhuman primate cloning and transgenesis using NT (Mitalipov et al., 2002a, 2002b; Ng et al., 2004; Simerly et al., 2004; Zhou et al., 2006).
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