TY - JOUR
T1 - C. elegans cell migration gene mig-10 shares similarities with a family of SH2 domain proteins and acts cell nonautonomously in excretory canal development
AU - Manser, James
AU - Roonprapunt, Chan
AU - Margolis, Ben
N1 - Funding Information:
We thank A. Coulson, J. Fleming, T. Hawkins, D. Livingstone, R. Shownkeen, J. Sulston, and E. Wolinsky for help, advice, and encouragement. We are especially grateful to J. Sulston for his exceptional contributions to this work, including construction of our DNA sequencing libraries. We are also very grateful to P. Mains (who is funded by the Medical Research Council of Canada) for providing lab space and other resources during J.M.'s visit to Calgary and to all members of the Mains and McGhee labs for their help and advice during that time. This work was supported by an NIH postdoctoral fellowship award to J.M. and by U.S. Army Breast Cancer Grant No. DAMD17-94-J-4075 to B.M. Some of the nematode strains used in our study were provided by the Caenorhabditis Genetics Center, which is funded by the NIH Center for Research Resources. B.M. is an investigator of the Howard Hughes Medical Institute.
PY - 1997/4/1
Y1 - 1997/4/1
N2 - The mig-10 gene of Caenorhabditis elegans is required for the long-range anteroposterior migration of embryonic neurons CAN, ALM, and HSN and proper development of the excretory canals. Here, we report the cloning and initial molecular characterization of mig-10. The predicted MIG-10 proteins share a large region of similarity with a recently identified family of mammalian SH2 domain proteins, Grb7 and Grb10. We call this region of similarity the GM region (for Grb and Mig). MIG-10 proteins do not contain an SH2 domain, but share with the Grbs a pleckstrin homology (PH) domain and proline-rich regions, features commonly found in signal transduction proteins. The functions of Grb7 and Grb10 are unknown, but Grb7 is overexpressed in certain breast cancers, where it is bound to the growth factor receptor HER2, while Grb10 has been implicated in insulin signaling. We also report the isolation of a new mig-10 (e2527) allele, as well as the molecular characterization of e2527 (splice acceptor mutation) and the canonical ct41 (amber) allele. Finally, we report the results of a genetic mosaic analysis which reveal that mig-10 acts cell nonautonomously in the development of the excretory canals and suggest a possible focus for mig-10 activity within descendants of the AB cell lineage. Elucidation of the role of mig-10 in C. elegans development should lead to a better understanding of cell migration and may shed light on the function of a family of SH2 domain proteins apparently involved in signal transduction and cancer.
AB - The mig-10 gene of Caenorhabditis elegans is required for the long-range anteroposterior migration of embryonic neurons CAN, ALM, and HSN and proper development of the excretory canals. Here, we report the cloning and initial molecular characterization of mig-10. The predicted MIG-10 proteins share a large region of similarity with a recently identified family of mammalian SH2 domain proteins, Grb7 and Grb10. We call this region of similarity the GM region (for Grb and Mig). MIG-10 proteins do not contain an SH2 domain, but share with the Grbs a pleckstrin homology (PH) domain and proline-rich regions, features commonly found in signal transduction proteins. The functions of Grb7 and Grb10 are unknown, but Grb7 is overexpressed in certain breast cancers, where it is bound to the growth factor receptor HER2, while Grb10 has been implicated in insulin signaling. We also report the isolation of a new mig-10 (e2527) allele, as well as the molecular characterization of e2527 (splice acceptor mutation) and the canonical ct41 (amber) allele. Finally, we report the results of a genetic mosaic analysis which reveal that mig-10 acts cell nonautonomously in the development of the excretory canals and suggest a possible focus for mig-10 activity within descendants of the AB cell lineage. Elucidation of the role of mig-10 in C. elegans development should lead to a better understanding of cell migration and may shed light on the function of a family of SH2 domain proteins apparently involved in signal transduction and cancer.
UR - http://www.scopus.com/inward/record.url?scp=0031128420&partnerID=8YFLogxK
U2 - 10.1006/dbio.1997.8516
DO - 10.1006/dbio.1997.8516
M3 - Article
C2 - 9142991
AN - SCOPUS:0031128420
SN - 0012-1606
VL - 184
SP - 150
EP - 164
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -