The basic helix-loop-helix transcription factors LIN-32 and HLH-2 function together in multiple steps of a C. elegans neuronal sublineage.
bHLH transcription factors function in neuronal development in organisms as diverse as worms and vertebrates. In the C. elegans male tail, a neuronal sublineage clonally gives rise to the three cell types (two neurons and a structural cell) of each sensory ray. We show here that the bHLH genes lin-32 and hlh-2 are necessary for the specification of multiple cell fates within this sublineage, and for the proper elaboration of differentiated cell characteristics. Mutations in lin-32, a member of the atonal family, can cause failures at each of these steps, resulting in the formation of rays that lack fully-differentiated neurons, neurons that lack cognate rays, and ray cells defective in the number and morphology of their processes. Mutations in hlh-2, the gene encoding the C. elegans E/daughterless ortholog, enhance the ray defects caused by lin-32 mutations. In vitro, LIN-32 can heterodimerize with HLH-2 and bind to an E-box-containing probe. Mutations in these genes interfere with this activity in a manner consistent with the degree of ray defects observed in vivo. We propose that LIN-32 and HLH-2 function as a heterodimer to activate different sets of targets, at multiple steps in the ray sublineage. During ray development, lin-32 performs roles of proneural, neuronal precursor, and differentiation genes of other systems.
Portman
D S
DS
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. portman@aecom.yu.edu
Emmons
S W
SW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D015342:DNA Probes / Q000235:genetics; D019281:Dimerization; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D017930:Genes, Reporter; D018257:Helix-Loop-Helix Motifs; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D013623:Tail / Q000254:growth & development; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D015342:DNA Probes; D015801:Helminth Proteins; D014157:Transcription Factors; C106514:HLH-2 protein, C elegans