Signal transduction and cell fate specification during C.elegans vulval development


A Wnt signal specifies the vulval equivalence group.

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The hermaphrodite vulva is a simple organ consisting of 22 cells that are formed during the postembryonic (larval) development. Towards the end of the first larval stage, a Wingless (Wnt) signal specifies the identity of the six equivalent vulval precursor cells (VPCs) P3.p through P8.p, that form the vulval equivalence group.
The Wnt signal induces the expression of the Hox gene l in-39 that specifies the vulval equivalence group and maintains the VPCs as polarized epithelial cells. Thus, the VPCs are competent to respond to an inductive signal that is produced later during vulval development.
At the beginning of the third larval stage, the fates of the vulval precursor cells are specified by the combined action of the RTK/RAS/MAP kinase and the LIN-12 Notch signaling pathways (figure). The gonadal anchor cell (AC) induces vulval differentiation. The AC produces the LIN-3 epidermal growth factor (EGF) that activates the receptor tyrosine kinase LET-23 (EGF receptor), in the closest VPC P6.p. This inductive signal is transduced in P6.p by the conserved RTK/RAS/MAP kinase signal

The combined action of the inductive and lateral signals induces the 1° and 2° vulval cell fates.

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transduction pathway where it specifies the primary (1°) vulval fate. In response to the inductive AC signal, P6.p generates a lateral signal that activates the LIN-12 Notch signaling pathway in its neighbors P5.p and P7.p. LIN-12 Notch signaling first inhibits the expression of the 1° fate (a process termed lateral inhibition). In a second step, LIN-12 Notch specifies the secondary (2°) fate in P5.p and P7.p. The VPCs that receive neither inductive nor lateral signals adopt the tertiary (3°) fate, they fuse with the epidermis (hyp7) after undergoing one round of cell divisions. After the 1° and 2° fates have been specified, the VPCs execute stereotypic patterns of cell divisions, and their descendants undergo extensive morphogenesis during the third and fourth larval stages. The cells migrate and invaginate to form the ventral opening, and several cell fusions between the differentiated vulval cells occur.