8. Gene expression during development

Different cells in an embryo express different sets of genes at different times. A common set of genes is present in all cells at all times and is called as the "House-keeping genes." These genes carry out the normal functions of a cell. Speciality genes are the special genes that enable a cell to carry out special functions. The genes responsible for embryonic body plan Homeobox genes, proto-oncogenes and PAX genes.

The gene expression is regulated by three sets of proteins called as the promoter, silencer and enhancer proteins. These proteins can modify the gene expression and define a particular cell type. There are also signaling proteins that facilitate the development of adjacent areas in a particular organ.

The SRY gene on the Y chromosome produces testis determining factor, which in turn activate the SOX9, and steroidogenesis factor (SF1) and it stimulates development of Sertoli and Leydig cells. WNT4 is the master gene for ovarian development. It inhibits SOX9 and up regulates DAX1. WNT4 along with other genes promotes formation of cortical cords and causes regression of medullary cords and prevents the tunica albuginea to develop [2].

ectodermal ridge (AER), which is a localized area of thickening on the surface ectoderm covering the limb bud, produces growth signals such as FGF4 and FGF8, which result in growth in proximal-distal axis. A collection of cells at the posterior margin of limb bud near body wall also undergoes proliferation to form the zone of polarizing activity which produce morphogen retinoic acid which in turn expresses SHH (Sonic Hedge Hog) which plays a huge role in determining the anteroposterior axis for limb development (Figure 9). Bones of the limb are derived by endochondral ossification of the parietal layer of the lateral plate mesoderm which is determined by HOX genes (HOXA and HOXD), which regulate the type, and shape of the bones. Digits are formed due to organized apoptosis of the AER into separate ridges and ultimately by interdigital apoptosis. HOXD13 mutations result in synpolydactyly, which is a dominantly inherited condition. Hand foot genital syndromes results from mutations of HOXA13 and presents hypospadias in males and bilateral thumb and great toe hypoplasia [6]. Dorsalization of the limb bud is under the control of genes like radical fringe and Wnt7a. Holt Oram syndrome an autosomal dominant inheritance is due to mutation of T-box 5 gene and is characterized by forelimb abnormalities and cardiac defects thus T-box genes determine the limb identity by activating FGFs. Another gene is the PitX, which contribute in forming hind limb characteristics [6].

Figure 9. Molecular regulation of limb development. Fibroblast growth factor 10 and AER initiate limb growth. These are induced by bone morphogenetic protein S (RA is retinoic acid, ZPA is zone of polarizing activity, AER is apical endoder-

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The most important feature in development of head and neck is the formation of pharyngeal arches resembling the gills of the fish. These arches are bars of mesenchyme tissue appearing at fourth or fifth week of development with an outer covering of ectoderm and inner layer of

10. Head and neck formation

mal ridge).

The extracellular growth factors regulate cell division and differentiation by the process of signal transduction and thus mutations in genes, which produce these factors and receptors, have been implicated in cancer development and also in developmental anomalies. The Fibroblast growth factor receptors (FGR) play an important role in embryogenesis. Mutations in FGR have been associated with two groups of disorders of skeletal system, which broadly include the craniosynostosis syndromes and achondroplasias. Genes such as Fibrillin-I and Elastin code for proteins that are needed for arranging microfibrils in the matrix and thus the mutations are associated with Marfans' syndrome [3].
