Developmental control of peripheral sense organs in Caenorhabditis elegans by a transcription factor of thebHLH family

Abstract

The nematode Caenorhabditis elegans is an excellent model system for the study of cell fate determination. The complete cell lineage of this organism has been elucidated, which reveals the developmental origins of all cells. Analysis in our laboratory of mutants affecting a set of male-specific sense organs known as rays has begun to reveal how cell fates are determined in the ray cell lineages, and how the specification of cell fates affects the ray pattern and morphology. The C. elegans lin-32 gene, which is the focus of this study, encodes a basic-helix-loop-helix (bHLH) protein, a class of transcription factors known to function in controlling cell type determination. lin-32 is both necessary and sufficient for specification of the ray neuroblast cell fate: its loss-of-function mutations transform the ray as well as several other neuroblasts into epidermal cells, while ectopic expression of lin-32 cDNA under the control of a heat shock promoter causes the generation of ectopic ray lineages. The null phenotype of lin-32 is lethality, probably because lin-32 is required for specifying many neuroblast cell fates during embryogenesis.;In order to determine how lin-32 activity is regulated, a lin-32 reporter gene was used to examine its expression pattern. The reporter gene is expressed in precursor cells that give rise to rays as well as in many other neuronal cells. Its expression in ray precursor cells is controlled by region-specific genes mab-5 and lin-22. Loss of lin-22 function results in anterior ectopic rays and ectopic expression of lin-32, while loss of mab-5 function results in loss of a subset of rays and loss of expression of lin-32 in those ray precursor cells. These two regulatory genes therefore restrict the generation of rays and the expression of lin-32 to a subset of cells in the tail.;LIN-32 is similar to Drosophila achaete-scute gene products and their homologs in vertebrates, all of which are known to function in neuronal cell type determination. The most similar protein is Drosophila atonal, which functions in expression of the neuroblast cell fate by precursor cells of chordotonal organs, and by the R8 photoreceptor of the eye. The similarity in structure and function of all these genes shows that basic mechanisms of cell type determination have been conserved through metazoan evolution.