title: Transcriptionally regulated cell adhesion network dictates distal tip cell directionality.
abstract: BACKGROUND
  The mechanisms that govern directional changes in cell migration are poorly understood. The migratory paths of two distal tip cells (DTC) determine the U-shape of the C. elegans hermaphroditic gonad. The morphogenesis of this organ provides a model system to identify genes necessary for the DTCs to execute two stereotyped turns.
  
  
  RESULTS
  Using candidate genes for RNAi knockdown in a DTC-specific strain, we identified two transcriptional regulators required for DTC turning: cbp-1, the CBP/p300 transcriptional coactivator homologue, and let-607, a CREBH transcription factor homologue. Further screening of potential target genes uncovered a network of integrin adhesion-related genes that have roles in turning and are dependent on cbp-1 and let-607 for expression. These genes include src-1/Src kinase, tln-1/talin, pat-2/α integrin and nmy-2, a nonmuscle myosin heavy chain.
  
  
  CONCLUSIONS
  Transcriptional regulation by means of cbp-1 and let-607 is crucial for determining directional changes during DTC migration. These regulators coordinate a gene network that is necessary for integrin-mediated adhesion. Overall, these results suggest that directional changes in cell migration rely on the precise gene regulation of adhesion.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey.
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Wong
authors.forename: William P
authors.initials: WP
authors.lastname: Kennedy
authors.forename: Jean E
authors.initials: JE
authors.lastname: Schwarzbauer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D006066:Gonads / Q000166:cytology / Q000196:embryology; D016023:Integrins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D016023:Integrins
keywords: C. elegans; cell migration; distal tip cell; hermaphrodite gonadogenesis; integrin