The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans.
In C. elegans, six lateral epidermal stem cells, the seam cells V1-V6, are located in a row along the anterior-posterior (A/P) body axis. Anterior seam cells (V1-V4) undergo a fairly simple sequence of stem cell divisions and generate only epidermal cells. Posterior seam cells (V5 and V6) undergo a more complicated sequence of cell divisions that include additional rounds of stem cell proliferation and the production of neural as well as epidermal cells. In the wild type, activity of the gene lin-22 allows V1-V4 to generate their normal epidermal lineages rather than V5-like lineages. lin-22 activity is also required to prevent additional neurons from being produced by one branch of the V5 lineage. We find that the lin-22 gene exhibits homology to the Drosophila gene hairy, and that lin-22 activity represses neural development within the V5 lineage by blocking expression of the posterior-specific Hox gene mab-5 in specific cells. In addition, in order to prevent anterior V cells from generating V5-like lineages, wild-type lin-22 gene activity must inhibit (directly or indirectly) at least five downstream regulatory gene activities. In anterior body regions, lin-22(+) inhibits expression of the Hox gene mab-5. It also inhibits the activity of the achaete-scute homolog lin-32 and an unidentified gene that we postulate regulates stem cell division. Each of these three genes is required for the expression of a different piece of the ectopic V5-like lineages generated in lin-22 mutants. In addition, lin-22 activity prevents two other Hox genes, lin-39 and egl-5, from acquiring new activities within their normal domains of function along the A/P body axis. Some, but not all, of the patterning activities of lin-22 in C. elegans resemble those of hairy in Drosophila.
Wrischnik
L A
LA
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0554, USA.
Kenyon
C J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D012734:Disorders of Sex Development / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000502:physiology; D005801:Genes, Homeobox / Q000502:physiology; D018257:Helix-Loop-Helix Motifs; D019476:Insect Proteins / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017933:Peripheral Nervous System / Q000196:embryology; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C084530:E(spl)mdelta-HLH protein, Drosophila; C107361:Lin-22 protein, C elegans