title: The Paired-box protein PAX-3 regulates the choice between lateral and ventral epidermal cell fates in C. elegans.
abstract: The development of the single cell layer skin or hypodermis of Caenorhabditis elegans is an excellent model for understanding cell fate specification and differentiation. Early in C. elegans embryogenesis, six rows of hypodermal cells adopt dorsal, lateral or ventral fates that go on to display distinct behaviors during larval life. Several transcription factors are known that function in specifying these major hypodermal cell fates, but our knowledge of the specification of these cell types is sparse, particularly in the case of the ventral hypodermal cells, which become Vulval Precursor Cells and form the vulval opening in response to extracellular signals. Previously, the gene pvl-4 was identified in a screen for mutants with defects in vulval development. We found by whole genome sequencing that pvl-4 is the Paired-box gene pax-3, which encodes the sole PAX-3 transcription factor homolog in C. elegans. pax-3 mutants show embryonic and larval lethality, and body morphology abnormalities indicative of hypodermal cell defects. We report that pax-3 is expressed in ventral P cells and their descendants during embryogenesis and early larval stages, and that in pax-3 reduction-of-function animals the ventral P cells undergo a cell fate transformation and express several markers of the lateral seam cell fate. Furthermore, forced expression of pax-3 in the lateral hypodermal cells causes them to lose expression of seam cell markers. We propose that pax-3 functions in the ventral hypodermal cells to prevent these cells from adopting the lateral seam cell fate. pax-3 represents the first gene required for specification solely of the ventral hypodermal fate in C. elegans providing insights into cell type diversification.
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: Kenneth.Thompson@medicine.ufl.edu.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Thompson
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: pradeep.m.joshi@lifesci.ucsb.edu.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Joshi
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: Jessica.Dymond@jhuapl.edu.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Dymond
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: gorrepati@ciwemb.edu.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Gorrepati
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 5 Center Drive, Bethesda, MD 20892, USA. Electronic address: smithhe2@niddk.nih.gov.
authors.forename: Harold E
authors.initials: HE
authors.lastname: Smith
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 5 Center Drive, Bethesda, MD 20892, USA. Electronic address: michaelkr@niddk.nih.gov.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Krause
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: eisenman@umbc.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Eisenmann
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology / Q000378:metabolism*; D005260:Female; D007814:Larva / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014844:Vulva / Q000166:cytology / Q000196:embryology / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D008164:Luminescent Proteins; C000610413:PAX-3 protein, C elegans; D051761:Paired Box Transcription Factors
keywords: C. elegans; Differentiation; Epidermis; Fate specification; Gene expression; PAX