The forkhead transcription factor UNC-130 is required for the graded spatial expression of the UNC-129 TGF-beta guidance factor in C. elegans.
Secreted proteins required for cellular movements along the circumference of the body wall in Caenorhabditis elegans include UNC-6/netrin and the novel TGF-beta UNC-129. Expression of these proteins is graded along the dorsoventral (D/V) axis, providing polarity information to guide migrations. Here we show that the graded expression of UNC-129 in dorsal but not ventral body muscles depends on unc-130, which encodes a Forkhead transcription factor. The phenotype of unc-130 mutants closely mimics the reported effects of ectopically expressing unc-129 in both dorsal and ventral body muscles (). This fits our present finding that unc-130 cell autonomously represses unc-129 expression in the ventral body muscles. Thus the cell-specific effects of unc-130 on ventral, but not dorsal, body muscle expression of unc-129 accounts for the D/V polarity information required for UNC-129-mediated guidance. Genetic interactions between unc-130 and other guidance genes show that several molecular pathways function in parallel to guide the ventral to dorsal migration of distal tip cells (DTCs) and axonal growth cones in C. elegans. Genetic interactions confirm that UNC-129 does not require the only known type II TGF-beta receptor in C. elegans (DAF-4) for its guidance functions. Also, unc-130 is partially required for male tail morphogenesis and for embryogenesis.
Nash
B
B
Department of Molecular and Medical Genetics, University of Toronto, Toronto M5S 1A8, Canada.
Colavita
A
A
Zheng
H
H
Roy
P J
PJ
Culotti
J G
JG
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins; D002450:Cell Communication; D002465:Cell Movement / Q000502:physiology*; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009132:Muscles / Q000196:embryology; D009417:Nerve Tissue / Q000196:embryology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000075385:Netrins; D009474:Neurons; D009479:Neuropeptides / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C117509:Dbl-1 protein, C elegans; D051858:Forkhead Transcription Factors; C489562:Foxd1 protein, mouse; C491100:Foxd3 protein, rat; D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; D009479:Neuropeptides; D018125:Receptors, Transforming Growth Factor beta; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C113622:UNC-129 protein, C elegans; C078146:UNC-6 protein, C elegans; C083704:daf-4 protein, C elegans; C415502:unc-130 protein, C elegans