T-box genes encode transcription factors involved in morphogenesis and organogenesis of invertebrates and vertebrates. The
mab-9 gene was the first member of the C. elegans T-box gene family to be identified.
mab-9 mutants are slightly uncoordinated (Unc) for backward movement, suggesting a role for
mab-9 in the nervous system, and they are defective in hindgut and male tail development. Ectopic, or mis-expression of
mab-9 is deleterious, hence this gene must be tightly regulated.. In order to identify upstream regulators of
mab-9, we have established a high-throughput genome-wide RNAi screen. We have focused on transformation in the pattern of
mab-9::GFP by RNAi silencing of 657 transcription factors, assuming that silencing of some transcription factors leads to a change of GFP expression in a strain of worms carrying an integrated
mab-9::GFP reporter. Our study suggests that the following genes have a strong effect in controlling
mab-9 expression:
nhr-23,
ldp-2,
nhr-22,
unc-4, Y45F3A.4,
nob-1,
nhr-112, and ZK1193.5. In addition, we have identified 62 other candidate genes with a possible role in
mab-9 regulation. One striking finding is that we have detected a lot of nuclear hormone receptor (NHRs) genes with a potential role in regulating
mab-9::GFP expression. By confirming those genes which are upstream of
mab-9, we hope to elucidate the genetic network in which
mab-9 operates.