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Proper development of vertebrate embryos depends not only on the crucial funtions of key evolutionarily conserved transcriptional regulators, but also on the precisely spatiotemporal expression of these transcriptional regulators. The mouse  Nolz-1 / Znf503/Zfp503  gene is a mammalian member of the conserved zinc-finger containing NET family. The expression pattern of  Nolz-1  in mouse embryos is highly correlated with that of its homologues in different species. To study the spatiotemporal regulation of  Nolz-1,  we first identified two evolutionarily conserved  cis -elements, UREA and UREB, in 5′ upstream regions of mouse  Nolz-1  locus. We then generated UREA- LacZ  and UREB- LacZ  transgenic reporter mice to characterize the putative enhancer activity of UREA and UREB. The results indicated that both UREA and UREB contained tissue-specific enhancer activity for directing  LacZ  expression in selective tissue organs during mouse embryogensis. UREA directed  LacZ  expression preferentially in selective regions of developing central nervous system, including the forebrain, hindbrain and spinal cord, whereas UREB directed  LacZ  expression mainly in other developing tissue organs such as the  Nolz-1  expressing branchial arches and its derivatives, the apical ectodermal ridge of limb buds and the urogenital tissues. Both UREA and UREB directed strong  LacZ  expression in the lateral plate mesoderm where endogenous  Nolz-1  was also expressed. Despite that the  LacZ  expression pattern did not full recapitulated the endogenous  Nolz-1  expression and some mismatched expression patterns were observed, co-expression of  LacZ  and  Nolz-1  did occur in many cells of selective tissue organs, such as in the ventrolateral cortex and ventral spinal cord of UREA-LacZ embryos, and the urogenital tubes of UREB-LacZ embryos. Taken together, our study suggests that UREA and UREB may function as evolutionarily conserved  cis -regulatory elements that coordinate with other  cis -elements to regulate spatiotemporal expression of  Nolz-1  in different tissue organs during mouse embryogenesis.

Identification of Two Evolutionarily Conserved 5' cis-Elements Involved in Regulating Spatiotemporal Expression of Nolz-1 during Mouse Embryogenesis