Temporal control of development is an important aspect of pattern formation that awaits complete molecular analysis. We identified lin-57 as a member of the C. elegans heterochronic gene pathway, which ensures that postembryonic developmental events are appropriately timed. Loss of lin-57 function causes the hypodermis to terminally differentiate and acquire adult character prematurely. lin-57 is hbl-1, revealing a role for the worm hunchback homolog in control of developmental time. Significantly, fly hunchback (hb) temporally specifies cell fates in the nervous system. The hbl-1/lin-57 3′UTR is required for postembryonic downregulation in the hypodermis and nervous system and contains multiple putative binding sites for temporally regulated microRNAs, including let-7. Indeed, we find that hbl-1/lin-57 is regulated by let-7, at least in the nervous system. Examination of the hb 3′UTR reveals potential binding sites for known fly miRNAs. Thus, evolutionary conservation of hunchback genes may include temporal control of cell fate specification and microRNA-mediated regulation.
Bibliographical noteFunding Information:
We thank D. Fay for generously supplying several hbl-1 reagents used in this study, J. Cahoy for analysis of hbl-1 homologs, R. Waterston for the MH27 antisera, the Twin Cities C. elegans Community for numerous discussions, and J. Simon, M. Titus, and J. Shaw for critical reading of the manuscript. Some strains were provided by the Caenorhabditis elegans Genetics Center. This work was supported by NIH grant HD08548 to J.E.A. and GM50227 to A.E.R.