Transcriptionally regulated cell adhesion network dictates distal tip cell directionality.

TitleTranscriptionally regulated cell adhesion network dictates distal tip cell directionality.
Publication TypeJournal Article
Year of Publication2014
AuthorsWong, M-C, Kennedy, WP, Schwarzbauer, JE
JournalDev Dyn
Volume243
Issue8
Pagination999-1010
Date Published2014 Aug
ISSN1097-0177
KeywordsAnimals, 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>

DOI10.1002/dvdy.24146
Alternate JournalDev. Dyn.
PubMed ID24811939
PubMed Central IDPMC4321954
Grant ListR01 GM059383 / GM / NIGMS NIH HHS / United States
U54 GM064346 / GM / NIGMS NIH HHS / United States
R01GM059383 / GM / NIGMS NIH HHS / United States