REF-1, a protein with two bHLH domains, alters the pattern of cell fusion in C. elegans by regulating Hox protein activity.
Hox genes control the choice of cell fates along the anteroposterior (AP) body axis of many organisms. In C. elegans, two Hox genes, lin-39 and mab-5, control the cell fusion decision of the 12 ventrally located Pn.p cells. Specific Pn.p cells fuse with an epidermal syncytium, hyp7, in a sexually dimorphic pattern. In hermaphrodites, Pn.p cells in the mid-body region remain unfused whereas in males, Pn.p cells adopt an alternating pattern of syncytial and unfused fates. The complexity of these fusion patterns arises because the activities of these two Hox proteins are regulated in a sex-specific manner. MAB-5 activity is inhibited in hermaphrodite Pn.p cells and thus MAB-5 normally only affects the male Pn.p fusion pattern. Here we identify a gene, ref-1, that regulates the hermaphrodite Pn.p cell fusion pattern largely by regulating MAB-5 activity in these cells. Mutation of ref-1 also affects the fate of other epidermal cells in distinct AP body regions. ref-1 encodes a protein with two basic helix-loop-helix domains distantly related to those of the hairy/Enhancer of split family. ref-1, and another hairy homolog, lin-22, regulate similar cell fate decisions in different body regions along the C. elegans AP body axis.
Alper
S
S
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143-0448, USA. alper@cgl.ucsf.edu
Kenyon
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002459:Cell Fusion; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D012734:Disorders of Sex Development; D005260:Female; D017238:Genes, Helminth; D005801:Genes, Homeobox; D018257:Helix-Loop-Helix Motifs; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D015801:Helminth Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C081538:Mab-5 protein, C elegans; C108673:lin-39 protein, C elegans; C428453:ref-1 protein, C elegans