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The C. elegans vulva is an established model system to understand how genes and pathways function to control organ formation. The precise mechanisms underlying vulval development are complex and require multiple layers of integration. These regulatory networks range from direct regulation of gene transcription through chromatin modification to activation or repression of downstream targets of signaling pathways. At the level of chromatin modification the C. elegans histone deacetylase, hda-l , plays an important role in repressing gene transcription. This work shows that hda-l mutants have defects in vulval invagination, morphogenesis, and gonadogenesis. Consistent with these phenotypes, hda-l is expressed in vulval cells and gonadal lineage cells in both C. elegans and C. briggsae. Furthermore, hda-l was found to regulate the expression of two transcription factors involved in uterine formation , lin-ll and egl-l3, and one gene involved in AC specification, zmp-l. hda-l also regulates fos-lb in vulval cells. With regards to cellular signaling we focused on the Wnt pathway component, pry-l/Axin. pry-l mutants are Muv and these ectopically induced VPCs in both C. elegans and C. briggsae adopt a secondary cell fate. This fate specification is independent of the gonad derived and LIN-12/Notch mediated lateral signals, indicating activated Wnt signaling alone can specify cell fates. pry-l mutants also exhibit a P7.p induction failure defect in both species . This defect is likely caused by LIN-l2 signaling resulting in persistent expression of the MAP kinase phosphatase, lip-l , in P7.p and P8.p. Further examination revealed that P7.p induction in pry-l ; lip-l and pry-l ; lin-l2 double mutants was significantly increased. These results are consistent with our hypothesis that crosstalk between Wnt and LIN-l2/Notch are crucial to proper vulval formation. These experiments provide evidence that vulval development is regulated by a complex regulatory network that is evolutionary conserved between C. elegans and C. briggsae. Master of Arts (MA) |
