In C. elegans the
dpy-20 gene was previously cloned by David Baillie group. They showed that it encodes a novel non-collagen protein, (Clark et al., 1995). Our group later reported that the
dpy-20 overexpresion suppresses transcription of alpha tubulin genes in the ventral cord motor neurons without affecting tubulin expression in other neurons located in the head and tail ganglia (Fukushige and Siddiqui, 1995). Northern blot analysis and
dpy-20::lacZ reporter gene expression in transgenic wild type animals showed that
dpy-20 is expressed not only in the hypodermal cells but also in a set of ventral cord neurons, and this expression is observed only during larval stages. Subsequent genetic experiments using loss of function
dpy-20 alleles and a number of mutants, such as those affected in the ventral cord motor neuron development shows that indeed
dpy-20 interacts with these genes. Similarly when
dpy-20::lacZ reporter gene was expressed in different mutant backgrounds (such as
unc-13 ,
unc-25 ,
unc-30 , and
unc-119 ), expression of
dpy-20 is clearly affected. These observations has lead us to propose that DPY-20 is a novel transcription regulator specific to motor neurons. Significant homology exists between the LIN-39 homeotic gene and the DPY-20 primary sequence. We have therefore sought to uncover
dpy-20 orthologs in Drosophila and mouse, and have isolated two independent genomic clones from a Drsophila genomic library in EMBL vector (kindly provided by Bob Holmgren). In situ hybridization of these clones show that one of them is distributed at two different locations in the fly genome, whereas the other clone hybridizes to a unique site. We are also screening Drosophila cDNA libraries made from larval and embryonic stages to identify fly cDNAs corresponding to the
dpy-20 gene. In a parallel experiment we have identified that mouse genome also contains
dpy-20 hybridizing sequences, which show a single band on Southern blot. We hope to identify the
dpy-20 homolog from Drosophila and study its role in motor neuron development. Sydney Brenner kindly encouraged the idea of searching for the
dpy-20 homologs, for which we remain grateful. We thank D. Baillie, D. Janke, H. Kose, Y. Hotta, Y. Kohara, R. Holmgren, Y. Yoshifumi, Y. Nishida, T. Matsuo, and Y. Ohshima for support.