title: MAB-10/NAB acts with LIN-29/EGR to regulate terminal differentiation and the transition from larva to adult in C. elegans.
abstract: In Caenorhabditis elegans, a well-defined pathway of heterochronic genes ensures the proper timing of stage-specific developmental events. During the final larval stage, an upregulation of the let-7 microRNA indirectly activates the terminal differentiation factor and central regulator of the larval-to-adult transition, LIN-29, via the downregulation of the let-7 target genes lin-41 and hbl-1. Here, we identify a new heterochronic gene, mab-10, and show that mab-10 encodes a NAB (NGFI-A-binding protein) transcriptional co-factor. MAB-10 acts with LIN-29 to control the expression of genes required to regulate a subset of differentiation events during the larval-to-adult transition, and we show that the NAB-interaction domain of LIN-29 is conserved in Kruppel-family EGR (early growth response) proteins. In mammals, EGR proteins control the differentiation of multiple cell lineages, and EGR-1 acts with NAB proteins to initiate menarche by regulating the transcription of the luteinizing hormone β subunit. Genome-wide association studies of humans and various studies of mouse recently have implicated the mammalian homologs of the C. elegans heterochronic gene lin-28 in regulating cellular differentiation and the timing of menarche. Our work suggests that human homologs of multiple C. elegans heterochronic genes might act in an evolutionarily conserved pathway to promote cellular differentiation and the onset of puberty.
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, 68-425, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Harris
authors.forename: H Robert
authors.initials: HR
authors.lastname: Horvitz
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051765:Early Growth Response Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008018:Life Cycle Stages / Q000235:genetics; D008297:Male; D008954:Models, Biological; D018978:Molting / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D051765:Early Growth Response Transcription Factors; C452195:LIN-28 protein, C elegans; C095571:LIN-29 protein, C elegans; C410586:LIN-41 protein, C elegans; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C562077:mab-10 protein, C elegans