The C. elegans heterochronic gene lin-46 affects developmental timing at two larval stages and encodes a relative of the scaffolding protein gephyrin.
The succession of developmental events in the C. elegans larva is governed by the heterochronic genes. When mutated, these genes cause either precocious or retarded developmental phenotypes, in which stage-specific patterns of cell division and differentiation are either skipped or reiterated, respectively. We identified a new heterochronic gene, lin-46, from mutations that suppress the precocious phenotypes caused by mutations in the heterochronic genes lin-14 and lin-28. lin-46 mutants on their own display retarded phenotypes in which cell division patterns are reiterated and differentiation is prevented in certain cell lineages. Our analysis indicates that lin-46 acts at a step immediately downstream of lin-28, affecting both the regulation of the heterochronic gene pathway and execution of stage-specific developmental events at two stages: the third larval stage and adult. We also show that lin-46 is required prior to the third stage for normal adult cell fates, suggesting that it acts once to control fates at both stages, and that it affects adult fates through the let-7 branch of the heterochronic pathway. Interestingly, lin-46 encodes a protein homologous to MoeA of bacteria and the C-terminal domain of mammalian gephyrin, a multifunctional scaffolding protein. Our findings suggest that the LIN-46 protein acts as a scaffold for a multiprotein assembly that controls developmental timing, and expand the known roles of gephyrin-related proteins to development.
Pepper
Anita S-R
AS
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
McCane
Jill E
JE
Kemper
Kevin
K
Yeung
Denise Au
DA
Lee
Rosalind C
RC
Ambros
Victor
V
Moss
Eric G
EG
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage; D003080:Cold Temperature; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D009154:Mutation; D010641:Phenotype; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C487428:Lin-46 protein, C elegans; D008565:Membrane Proteins; C073441:gephyrin