LIN-39 and the EGFR/RAS/MAPK pathway regulate C. elegans vulval morphogenesis via the VAB-23 zinc finger protein
Pellegrino, Mark W.The University of Melbourne, Department of Veterinary Science, Werribee, Victoria, Australia - University of Zürich, Institute of Molecular Life Sciences, Switzerland
Farooqui, SarfarazhussainUniversity of Zürich, Institute of Molecular Life Sciences, Switzerland - PhD Program in Molecular Life Sciences UNI ETH Zürich, Switzerland
Fröhli, ErikaUniversity of Zürich, Institute of Molecular Life Sciences, Switzerland
Rehrauer, HubertThe Functional Genomics Center, UNI ETH Zürich, Switzerland
English
Morphogenesis represents a phase of development during which cell fates are executed. The conserved hox genes are key cell fate determinants during metazoan development, but their role in controlling organ morphogenesis is less understood. Here, we show that the C. elegans hox gene lin-39 regulates epidermal morphogenesis via its novel target, the essential zinc finger protein VAB-23. During the development of the vulva, the egg-laying organ of the hermaphrodite, the EGFR/RAS/MAPK signaling pathway activates, together with LIN-39 HOX, the expression of VAB-23 in the primary cell lineage to control the formation of the seven vulval toroids. VAB-23 regulates the formation of homotypic contacts between contralateral pairs of cells with the same sub-fates at the vulval midline by inducing smp-1 (semaphorin) transcription. In addition, VAB-23 prevents ectopic vulval cell fusions by negatively regulating expression of the fusogen eff-1. Thus, LIN-39 and the EGFR/RAS/MAPK signaling pathway, which specify cell fates earlier during vulval induction, continue to act during the subsequent phase of cell fate execution by regulating various aspects of epidermal morphogenesis. Vulval cell fate specification and execution are, therefore, tightly coupled processes.