title: Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure and Caenorhabditis elegans Gastrulation.
abstract: Neural tube defects including spina bifida are common and severe congenital disorders. In mice, mutations in more than 200 genes can result in neural tube defects. We hypothesized that this large gene set might include genes whose homologs contribute to morphogenesis in diverse animals. To test this hypothesis, we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a topologically similar process to vertebrate neural tube closure. Both C. elegans gastrulation and vertebrate neural tube closure involve the internalization of surface cells, requiring tissue-specific gene regulation, actomyosin-driven apical constriction, and establishment and maintenance of adhesions between specific cells. Our screen identified several neural tube defect gene homologs that are required for gastrulation in C. elegans, including the transcription factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early endodermally expressed genes as well as genes expressed in other early cell lineages, establishing sptf-3 as a key contributor to multiple well-studied C. elegans cell fate specification pathways. We also identified members of the actin regulatory WAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of WAVE complex members reduced the narrowing of endodermal cells' apical surfaces. Although WAVE complex members are expressed broadly in C. elegans, we found that expression of a vertebrate WAVE complex member, nckap1, is enriched in the developing neural tube of Xenopus. We show that nckap1 contributes to neural tube closure in Xenopus. This work identifies in vivo roles for homologs of mammalian neural tube defect genes in two manipulable genetic model systems.
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599 Department of Biology, West Chester University, West Chester, Pennsylvania 19383 jsullivan-brown@wcupa.edu.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Sullivan-Brown
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Panna
authors.initials: P
authors.lastname: Tandon
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Kim E
authors.initials: KE
authors.lastname: Bird
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Dickinson
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Sophia C
authors.initials: SC
authors.lastname: Tintori
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Heppert
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Joy H
authors.initials: JH
authors.lastname: Meserve
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Trogden
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Orlowski
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Conlon
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, North Carolina 27599 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, North Carolina 27599.
authors.forename: Bob
authors.initials: B
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002453:Cell Cycle; D002462:Cell Membrane; D047108:Embryonic Development / Q000235:genetics; D004707:Endoderm / Q000378:metabolism; D054262:Gastrulation / Q000235:genetics; D017238:Genes, Helminth; D006801:Humans; D009024:Morphogenesis / Q000235:genetics*; D054259:Neural Tube / Q000196:embryology*; D034622:RNA Interference; D018510:RNA, Helminth; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics; D014714:Vertebrates / Q000196:embryology / Q000235:genetics; D014982:Xenopus laevis
chemical_list: D029742:Caenorhabditis elegans Proteins; C450822:GEX-3 protein, C elegans; D018510:RNA, Helminth; D014157:Transcription Factors; C532811:wve-1 protein, C elegans
keywords: C. elegans; Morphogenesis; gastrulation