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Genetics January 1, 2016; 202 (1): 123-39.

Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure and Caenorhabditis elegans Gastrulation.

Sullivan-Brown JL , Tandon P , Bird KE , Dickinson DJ , Tintori SC , Heppert JK , Meserve JH , Trogden KP , Orlowski SK , Conlon FL , Goldstein B .

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.

PubMed ID: 26434722
PMC ID: PMC4701080
Article link: Genetics
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: apaf1 cfl1 nckap1 pfn1
Antibodies: GFP Ab14 Ptpn11 Ab1

Disease Ontology terms: neural tube defect
References [+] :
Anders, HTSeq--a Python framework to work with high-throughput sequencing data. 2015, Pubmed