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.
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. eleganshermaphroditic 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: B Sönnichsen; L B Koski; A Walsh; P Marschall; B Neumann; M Brehm; A-M Alleaume; J Artelt; P Bettencourt; E Cassin; M Hewitson; C Holz; M Khan; S Lazik; C Martin; B Nitzsche; M Ruer; J Stamford; M Winzi; R Heinkel; M Röder; J Finell; H Häntsch; S J M Jones; M Jones; F Piano; K C Gunsalus; K Oegema; P Gönczy; A Coulson; A A Hyman; C J Echeverri Journal: Nature Date: 2005-03-24 Impact factor: 49.962
Authors: Takehiro Kawano; Hong Zheng; David C Merz; Yuji Kohara; Katsuyuki K Tamai; Kiyoji Nishiwaki; Joseph G Culotti Journal: Development Date: 2009-03-18 Impact factor: 6.868
Authors: Christelle Gally; Frédéric Wissler; Hala Zahreddine; Sophie Quintin; Frédéric Landmann; Michel Labouesse Journal: Development Date: 2009-08-12 Impact factor: 6.868
Authors: John S Reece-Hoyes; Jane Shingles; Denis Dupuy; Christian A Grove; Albertha J M Walhout; Marc Vidal; Ian A Hope Journal: BMC Genomics Date: 2007-01-23 Impact factor: 3.969
Authors: Lara M Linden; Kacy L Gordon; Ariel M Pani; Sara G Payne; Aastha Garde; Dane Burkholder; Qiuyi Chi; Bob Goldstein; David R Sherwood Journal: Dev Biol Date: 2017-06-23 Impact factor: 3.582