How is the nodal signaling pathway established during early embryogenesis? MATER

Question

How is the nodal signaling pathway established during early embryogenesis?

MATERIALS AND METHODS Generation of the mutation A positive/negative targeting vector Mansour et al., 1988) was designed so as to delete a large portion of the Notchl gene. Genomic DNA comesponding to the Notchl locus was isolated from a 129/Sv genomic library. Regions ofhomology of 6.1 and 1.1 kb were cloned on either side of the neomycin resistance gene driven by the PGKi promoter. The HSV thymidine kinase gene, also with a PGK1 promoter, was cloned 3' of the shorter am of homology. A success ful recombination and replacement event would result in the acquisi- tion of neomycin resistance, gancyclovir sensitivity, and the deletion of 10.4 kb of the Notchl gene Fig. 1). The ES cell line used elec- troporation was R1-S3 (Nagy et al., 1993). The targeting event was verified by Southem analysis with probes from the Notchl gene extemal to the targeting vector on both sides, and from within the deletion (Fig. 1 and not shown) Chimeras were generated by blastocyst injection with two targeted

Explanation / Answer

During early development of embryo, nodal signalling pathway plays an important role in pattern formation of the embryo.There are present proteins that belong to nodal family and are known as nodal family of proteins.When these proteins bind to activin and activin like receptors, phosphorylation of Smad 2 takes place.Phosphorylated Smad 2 along with Smad 4 forms a complex and this complex is translocated to the nucleus where it binds with  transcription factors i.e FoxH1, p53 and mixer leading to the induction of genes such as Nodal, Lefty, the antagonist of nodal Cerberus etc.Induction of these genes induces the formation of mesoderm and endoderm,anterior posterior axis positioning and left right specification of axis. EGF-CFC cofactors and antagonists of the Lefty and Cerberus families of proteins regulate the nodal signalling pathway extracellularly.

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