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Dev Dyn. 2014 Aug;243(8):999-1010. doi: 10.1002/dvdy.24146. Epub 2014 May 26.

Transcriptionally regulated cell adhesion network dictates distal tip cell directionality.

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  • 1Department of Molecular Biology, Princeton University, Princeton, New Jersey.

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.

KEYWORDS:

C. elegans; cell migration; distal tip cell; hermaphrodite gonadogenesis; integrin

PMID:
24811939
PMCID:
PMC4321954
DOI:
10.1002/dvdy.24146
[PubMed - indexed for MEDLINE]
Free PMC Article
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