5. Cell signaling

end of the embryo. Nodal which is a protein of transforming growth factor beta family

Another important protein of Transforming growth factor beta is Bone Morphogenic Protein 4, which is secreted throughout the embryonic disc. This is important for ventralising mesoderm for kidney, blood and body wall development through the formation of lateral plate and intermediate mesoderm. The primitive node acts as an organizer and inhibits action of Bone Morphogenic Protein 4 by promoting other genes. Chordin, noggin and follistatin antagonize the action of BMP4. This results in dorsalisation of cranial mesoderm to form notochord,

Brachyury T gene regulates the dorsal mesoderm formation in middle and caudal regions of the embryo. Laterality, i.e., left -right -sidedness is development by the interaction of signal molecules and genes. Genes regulating left side development are well known like LEFTY-2, Nodal that up regulates PITX2, which is a transcription factor. A neurotransmitter serotonin (5HT) also plays an important role in establishing left sidedness in the embryo. Defects of Lefty-2 and PITX2 and 5 HT can lead to defects like dextrocardia, situs inversus and cardiac

The cells of the epiblast, the regions of streak and node from they migrate determines the fate and the type of mesoderm they will eventually form. The cells which migrate from cranial end of node form the notochord and prochordal plate. The cells that proliferate and migrate from lateral edges of the node and cranial part of primitive streak form the paraxial mesoderm. The cells that proliferate and migrate from middle of primitive streak form the intermediate mesoderm. The cells migrating from caudal part of the streak form the lateral plate mesoderm. The cells from the caudal most part of the streak contribute to extra embryonic mesoderm. Thus the fate map of development of various organ systems is established at the time of

Genes are not only carriers of inherited information but also they are extremely important instructors for embryological development. In the last decade there is a tremendous progress in identifying specific genes, which are responsible for control of development in human embryo. The earlier studies were initially performed in Drosophila and other laboratory animals have immensely contributed in understanding the pathways and genes involved in

There are genes, which are involved in development of code for proteins, which include signaling molecules and receptors, DNA transcription factors, enzymes, transport systems and components of extracellular matrix. Thus mutations and defects in all of the mentioned factors above

The genetic factors which initiate, maintain and establish embryonic development is not clearly determined yet. There are some key developmental pathways, which are identified

establishes and maintains the primitive streak.

somites and somatomeres.

80 Genetic Diversity and Disease Susceptibility

abnormalities.

gastrulation itself [2].

human development.

can lead to birth defects [3].

4. Genes as carriers of information

Cell signaling plays a very important role in in normal embryogenesis. The receptor tyrosine kinase (RTK) signaling phosphorylates tyrosine residues and is activated by ligands and thus brings about diverse functions during development. Certain ligands, which activate RTK, are fibroblast growth factor (FGF), epidermal growth factor, TGF, Platelet derived growth factor, etc. The intracellular cascade of reactions that follows once binding of ligands activates the receptors has been studied in vitro experiments and is believed to bring about multiple changes though not fully understood [4].

The TGF-beta family of signaling molecules constitutes at least 33 members of this cytokine family. They are involved in cross talk between cells thus establish cellular communication. These extracellular signaling polypeptides are transduced to regulate other gene expression. These signaling molecules bind to the receptors on the cell surface brings about a cascade of reactions and activation of receptor kinases which leads to translocation of complexes into nucleus of cells and thus either activate or suppress the target gene expression.

The TGF-beta family can be grouped into (1) the BMPs and (2) TGF-beta s, activin, nodal, and myostatin. These groups of signaling molecules are actively involved in various cellular and developmental processes like cell cycle, cell migration, cell size, gastrulation and axis specification and various metabolic processes. BMP signaling is also involved in dendritogenesis and axonal transport.
