TY - JOUR
T1 - Mig-38, a novel gene that regulates distal tip cell turning during gonadogenesis in C. elegans hermaphrodites
AU - Martynovsky, Maria
AU - Wong, Ming Ching
AU - Byrd, Dana T.
AU - Kimble, Judith
AU - Schwarzbauer, Jean E.
N1 - Funding Information:
We thank Hongyu Shang for critical reading of the manuscript and valuable suggestions, Joe Goodhouse for his help with microscopy, R. Daniel Slone for technical help, and Andrew Fire (Stanford University, Stanford, CA) for the L4817 vector. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR). Funding was provided to JES by NIH R01GM059383 and by the Cell Migration Consortium GLUE Grant no. NIH U54 GM064346 . MM was supported by the NIH pre-doctoral training Grant no. 5T32GM007388 . MCW was a postdoctoral fellow of the New Jersey Commission on Cancer Research.
PY - 2012/8/15
Y1 - 2012/8/15
N2 - In Caenorhabditis elegans gonad morphogenesis, the final U-shapes of the two hermaphrodite gonad arms are determined by migration of the distal tip cells (DTCs). These somatic cells migrate in opposite directions on the ventral basement membrane until specific extracellular cues induce turning from ventral to dorsal and then centripetally toward the midbody region on the dorsal basement membrane. To dissect the mechanism of DTC turning, we examined the role of a novel gene, F40F11.2/mig-38, whose depletion by RNAi results in failure of DTC turning so that DTCs continue their migration away from the midbody region. mig-38 is expressed in the gonad primordium, and expression continues throughout DTC migration where it acts cell-autonomously to control DTC turning. RNAi depletion of both mig-38 and ina-1, which encodes an integrin adhesion receptor, enhanced the loss of turning phenotype indicating a genetic interaction between these genes. Furthermore, the integrin-associated protein MIG-15/Nck-interacting kinase (NIK) works with MIG-38 to direct DTC turning as shown by mig-38 RNAi with the mig-15(rh80) hypomorph. These results indicate that MIG-38 enhances the role of MIG-15 in integrin-dependent DTC turning. Knockdown of talin, a protein that is important for integrin activation, causes the DTCs to stop migration prematurely. When both talin and MIG-38 were depleted by RNAi treatment, the premature stop phenotype was suppressed. This suppression effect was reversed upon additional depletion of MIG-15 or its binding partner NCK-1. These results suggest that both talin and the MIG-15/NCK-1 complex promote DTC motility and that MIG-38 may act as a negative regulator of the complex. We propose a model to explain the dual role of MIG-38 in motility and turning.
AB - In Caenorhabditis elegans gonad morphogenesis, the final U-shapes of the two hermaphrodite gonad arms are determined by migration of the distal tip cells (DTCs). These somatic cells migrate in opposite directions on the ventral basement membrane until specific extracellular cues induce turning from ventral to dorsal and then centripetally toward the midbody region on the dorsal basement membrane. To dissect the mechanism of DTC turning, we examined the role of a novel gene, F40F11.2/mig-38, whose depletion by RNAi results in failure of DTC turning so that DTCs continue their migration away from the midbody region. mig-38 is expressed in the gonad primordium, and expression continues throughout DTC migration where it acts cell-autonomously to control DTC turning. RNAi depletion of both mig-38 and ina-1, which encodes an integrin adhesion receptor, enhanced the loss of turning phenotype indicating a genetic interaction between these genes. Furthermore, the integrin-associated protein MIG-15/Nck-interacting kinase (NIK) works with MIG-38 to direct DTC turning as shown by mig-38 RNAi with the mig-15(rh80) hypomorph. These results indicate that MIG-38 enhances the role of MIG-15 in integrin-dependent DTC turning. Knockdown of talin, a protein that is important for integrin activation, causes the DTCs to stop migration prematurely. When both talin and MIG-38 were depleted by RNAi treatment, the premature stop phenotype was suppressed. This suppression effect was reversed upon additional depletion of MIG-15 or its binding partner NCK-1. These results suggest that both talin and the MIG-15/NCK-1 complex promote DTC motility and that MIG-38 may act as a negative regulator of the complex. We propose a model to explain the dual role of MIG-38 in motility and turning.
KW - C. elegans
KW - Cell migration
KW - Distal tip cell
KW - Hermaphrodite gonadogenesis
KW - Integrin
KW - Mig-38
UR - http://www.scopus.com/inward/record.url?scp=84864041025&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864041025&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2012.06.011
DO - 10.1016/j.ydbio.2012.06.011
M3 - Article
C2 - 22732572
AN - SCOPUS:84864041025
SN - 0012-1606
VL - 368
SP - 404
EP - 414
JO - Developmental biology
JF - Developmental biology
IS - 2
ER -