The Caenorhabditis elegans heterochronic gene pathway controls stage-specific transcription of collagen genes.
In Caenorhabditis elegans, the terminal differentiation of the hypodermal cells occurs at the larval-to-adult molt, and is characterized in part by the formation of a morphologically distinct adult cuticle. The timing of this event is controlled by a pathway of heterochronic genes that includes the relatively direct regulatory gene, lin-29, and upstream genes lin-4, lin-14 and lin-28. Using northern analysis to detect endogenous collagen mRNA levels and collagen/lacZ reporter constructs to monitor collagen transcriptional activity, we show that the stage-specific switch from larval cuticle to adult cuticle correlates with the transcriptional activation of adult-specific collagen genes and repression of larval-specific collagen genes. Heterochronic mutations that cause precocious formation of adult cuticle also cause precocious transcription of the adult-specific collagen genes, col-7 and col-19; heterochronic mutations that prevent the switch to adult cuticle cause continued expression of the larval collagen gene, col-17, in adults and prevent adult-specific activation of col-7 or col-19. A 235 bp segment of col-19 5' sequences is sufficient to direct the adult-specific expression of a col-19/lacZ reporter gene in hypodermal cells. These findings indicate that the heterochronic gene pathway regulates the timing of hypodermal cell terminal differentiation by regulating larval- and adult-specific gene expression, perhaps by the direct action of lin-29.
Liu
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Z
Harvard University Department of Cellular and Developmental Biology, Cambridge, MA 02138, USA.
Kirch
S
S
Ambros
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V
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D003094:Collagen / Q000235:genetics*; D018509:DNA, Helminth; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D017930:Genes, Reporter; D007763:Lac Operon; D007814:Larva; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D015345:Oligonucleotide Probes; D014158:Transcription, Genetic
D018509:DNA, Helminth; D015345:Oligonucleotide Probes; D003094:Collagen