lin-35/Rb and the CoREST ortholog spr-1 coordinately regulate vulval morphogenesis and gonad development in C. elegans.
Using a genetic screen to identify genes that carry out redundant functions during development with lin-35/Rb, the C. elegans Retinoblastoma family ortholog, we have identified a mutation in spr-1. spr-1 encodes the C. elegans ortholog of human CoREST, a protein containing Myb-like SANT and ELM2 domains, which functions as part of a transcriptional regulatory complex. CoREST recruits mediators of transcriptional repression, including histone deacetylase, and demethylase, and interacts with the tumor suppression protein REST. spr-1/CoREST was previously shown in C. elegans to suppress defects associated with loss of the presenilin sel-12, which functions in the proteolytic processing of LIN-12/Notch. Here we show that lin-35 and spr-1 coordinately regulate several developmental processes in C. elegans including the ingression of vulval cells as well as germline proliferation. We also show that loss of lin-35 and spr-1 hypersensitizes animals to a reduction in LIN-12/Notch activity, leading to the generation of proximal germline tumors. This defect, which is observed in lin-35; spr-1; lin-12(RNAi) and lin-35; spr-1; hop-1(RNAi) triple mutants is likely due to a delay in the entry of germ cells into meiosis.
Bender
Aaron M
AM
University of Wyoming, College of Agriculture, Department of Molecular Biology, Department 3944, 1000 E. University Avenue, Laramie, WY 82071, USA.
Kirienko
Natalia V
NV
Olson
Sara K
SK
Esko
Jeffery D
JD
Fay
David S
DS
D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002807:Chondroitin / Q000096:biosynthesis; D005260:Female; D005854:Germ Cells / Q000502:physiology; D006066:Gonads / Q000254:growth & development / Q000502:physiology; D007814:Larva; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D023421:Models, Animal; D009024:Morphogenesis; D009154:Mutation; D009373:Neoplasms, Germ Cell and Embryonal / Q000473:pathology; D051880:Receptors, Notch / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014844:Vulva / Q000254:growth & development / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; C116485:lin-35 protein, C elegans; D002807:Chondroitin