Title | Transcriptionally regulated cell adhesion network dictates distal tip cell directionality. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Wong, M-C, Kennedy, WP, Schwarzbauer, JE |
Journal | Dev Dyn |
Volume | 243 |
Issue | 8 |
Pagination | 999-1010 |
Date Published | 2014 Aug |
ISSN | 1097-0177 |
Keywords | Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Adhesion, Cell Movement, Gonads, Integrins |
Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
DOI | 10.1002/dvdy.24146 |
Alternate Journal | Dev Dyn |
PubMed ID | 24811939 |
PubMed Central ID | PMC4321954 |
Grant List | R01 GM059383 / GM / NIGMS NIH HHS / United States U54 GM064346 / GM / NIGMS NIH HHS / United States R01GM059383 / GM / NIGMS NIH HHS / United States |