title: LIN-39 and the EGFR/RAS/MAPK pathway regulate C. elegans vulval morphogenesis via the VAB-23 zinc finger protein.
abstract: 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.
authors: The University of Melbourne, Department of Veterinary Science, Werribee, Victoria, Australia.
authors: Mark W
authors: MW
authors: Pellegrino
authors: Sarfarazhussain
authors: S
authors: Farooqui
authors: Erika
authors: E
authors: Fröhli
authors: Hubert
authors: H
authors: Rehrauer
authors: Stéphanie
authors: S
authors: Kaeser-Pebernard
authors: Fritz
authors: F
authors: Müller
authors: Robin B
authors: RB
authors: Gasser
authors: Alex
authors: A
authors: Hajnal
mesh_terms: D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000033:anatomy & histology* / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002459:Cell Fusion; D019070:Cell Lineage; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D039961:Semaphorins; D014157:Transcription Factors; C546344:VAB-23 protein, C elegans; C418523:ceh-20 protein, C elegans; C108673:lin-39 protein, C elegans; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases