bHLH transcription factors function in neuronal development

The development of the multiple cell types of a metazoan organism requires that precursor cells pass through a variety of intermediate cell states as cells become progressively more restricted in their developmental potential. Much remains unknown about how intermediate cell states are established during development, and how the restricted potentials of intermediates allows well-ordered transitions between states. Understanding how signals and transcription factors orchestrate changes in gene expression, and hence changes in cell states, is a major area of interest in developmental biology. One experimental approach to addressing these questions is to study a developmental sublineage, in which the generation of multiple cell types is coupled together through the use of a stereotyped pattern of division and differentiation. A sublineage may represent a series of cell state transitions intrinsically programmed into a precursor (Chalfie et al., 1981; Sternberg and Horvitz, 1982; Sulston and Horvitz, 1977), in which a single cell gives rise to distinct differentiated progeny with fixed relative frequencies. Nematode development provides a number of examples of such sublineages, particularly in the ventral hypodermal lineages that give rise to ventral cord neurons and the vulva, and in the lateral hypodermal development of seam cells and the male tail rays (Chalfie et al., 1981; Sulston and Horvitz, 1977; Sulston et al., 1983). A lineage very similar to that which generates the rays occurs in the development of external sensory organs in Drosophila (Jan and Jan, 1994; Gho et al., 1999; Reddy and Rodrigues, 1999); although this program is not cell-autonomous, as it is in C. elegans, its similarity indicates that it may be derived from the same ancestral sublineage. In addition, development of the sensory patches in the vertebrate inner ear has been proposed to employ a similar lineage-based strategy (Adam et al., 1998), and vertebrate CNS development may use defined sublineages (Qian et al., 1998), suggesting that the use of sublineages to control cell state transitions may be a widespread developmental theme. Studying a well-defined sublineage in a genetic system provides a unique opportunity to dissect the requirements for individual cell states, state transitions, asymmetric divisions, and the establishment of differentiated cell fates by the sublineage’s postmitotic descendants. The ray sublineage in the C. elegans male tail is executed by each of nine pairs of hypodermal ray precursor cells, giving rise to nine rays on each side of the mature animal (Sulston and Horvitz, 1977). Each ray is a small sensillum containing two neurons and a structural cell. Together, the rays function to sense the hermaphrodite during the mating process (Emmons and Sternberg, 1997; Emmons, 1999). Specification of the ray neuroblasts has been shown to require the gene lin32, a basic-helix-loop-helix (bHLH) transcription factor of the atonal family (Zhao and Emmons, 1995). lin-32 has been proposed to serve a proneural function for the ray precursor cells, making them competent to become neuroblasts. Since 5415 Development 127, 5415-5426 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV9752