Concepts of Developmental Biology

Figure 14-8 The clinical consequences of dysregulated growth in a child with Proteus syndrome, a congenital segmental overgrowth disorder affecting his face, abdomen, and right leg. Affected children are usually normal-appearing at birth but then in the first year begin to develop asymmetrical and disproportionate overgrowth of body parts. There are multiple malformations of the vascular system, including veins, capillaries and lymphatics; the osseous skeleton; and the connective tissue. The disorder is caused by somatic mosaicism for de novo activating mutations in AKT1, encoding a cell growth–promoting protein, which explains why the condition is always sporadic and occurs in an irregular pattern throughout the body in different affected individuals. See Sources & Acknowledgments.

Morphogenesis is accomplished in the developing organism by the coordinated interplay of the mechanisms introduced in this section. In some contexts, morphogenesis is used as a general term to describe all of development, but this is formally incorrect because morphogenesis has to be coupled to the process of growth discussed here to generate a normally shaped and functioning tissue or organ.

Human Embryogenesis


Figure 14-9 Human development begins with cleavage of the fertilized egg. A, The fertilized egg at day 0 with two pronuclei and the polar bodies. B, A two-cell embryo at day 1 after fertilization. C, A four-cell embryo at day 2. D, The eight-cell embryo at day 3. E, The 16-cell stage later in day 3, followed by the phenomenon of compaction, whereby the embryo is now termed a morula (F, day 4). G, T formation of the blastocyst at day 5, with the inner cell mass indicated by the arrow. Finally, the embryo (arrow) hatches from the zona pellucida (H). See Sources & Acknowledgments.


Figure 14-10 Cell lineage and fate during preimplantation development. Embryonic age is given in time after fertilization in humans: A, 6 days. B, 7 days. C, 8 days post fertilization. See Sources & Acknowledgments.

The embryo implants in the endometrial wall of the uterus in the interval between days 7 and 12 after fertilization. After implantation, gastrulation occurs, in which cells rearrange themselves into a structure consisting of three cellular compartments, termed the germ layers, comprising the ectoderm, mesoderm, and endoderm. The three germ layers give rise to different structures. The endodermal lineage forms the central visceral core of the organism. This includes the cells lining the main gut cavity, the airways of the respiratory system, and other similar structures. The mesodermal lineage gives rise to kidneys, heart, vasculature, and structural or supportive functions in the organism. Bone and muscle are nearly exclusively mesodermal and have the two main functions of structure (physical support) and providing the necessary physical and nutritive support of the hematopoietic system. The ectoderm gives rise to the central and peripheral nervous systems and the skin. During the complicated movements that occur in gastrulation, the embryo also establishes the major axes of the final body plan: anterior-posterior (cranial-caudal), dorsal-ventral (back-front), and left-right axes, which are discussed later.

The next major stages of development involve the initiation of the nervous system, establishment of the basic body plan, and then organogenesis, which occupies weeks 4 to 8. The position and basic structures of all of the organs are now established, and the cellular components necessary for their full development are now in place. It is during this phase of embryonic development that neural tube defects occur, as we explore next.

Neural Tube Defects

As a group, NTDs are a leading cause of stillbirth, death in early infancy, and handicap in surviving children. Their incidence at birth is variable, ranging from almost 1% in Ireland to 0.2% or less in the United States. The frequency also appears to vary with social factors and season of birth and oscillates widely over time (with a marked decrease in recent years; see later discussion).

A small proportion of NTDs have known specific causes, for example, amniotic bands (see Fig. 14-3), some single-gene defects with pleiotropic expression, some chromosomal disorders, and some teratogens. Most NTDs, however, are isolated defects of unknown cause.

Maternal Folic Acid Deficiency and Neural Tube Defects.

The mutant allele is so common in many populations that between 5% and 15% of the population is homozygous for the variant. In studies of infants with NTDs and their mothers, it was found that mothers of infants with NTDs were twice as likely as controls to be homozygous for the mutant allele encoding the unstable enzyme. How this enzyme defect contributes to NTDs and whether the abnormality is a direct result of elevated homocysteine levels, depressed methionine levels, or some other metabolic derangement remain undefined.

Prevention of Neural Tube Defects.

The second approach is to apply prenatal screening for all pregnancies and offer prenatal diagnosis to high-risk pregnancies. Prenatal diagnosis of anencephaly and most cases of open spina bifida relies on detecting excessive levels of alpha-fetoprotein (AFP) and other fetal substances in the amniotic fluid and by ultrasonographic scanning, as we shall discuss further in Chapter 17. However, less than 5% of all patients with NTDs are born to women with previous affected children. For this reason, screening of all pregnant women for NTDs by measurements of AFP and other fetal substances in maternal serum is now widespread. Thus we can anticipate that a combination of preventive folic acid therapy and maternal AFP screening will provide major public health benefits by drastically reducing the incidence of NTDs.

Human Fetal Development

The Germ Cell: Transmitting Genetic Information

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Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Concepts of Developmental Biology

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