Abstract
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.
Highlights
IntroductionNolz-1, the Drosophila nocA like zinc-finger gene-1 ( know as Znf503 or Zfp503 by Genome Informatics), is a member of the SP1-related nocA/elb/tlp-1 (NET) family
Nolz-1, the Drosophila nocA like zinc-finger gene-1, is a member of the SP1-related nocA/elb/tlp-1 (NET) family
Our study suggests that UREA and UREB may function as evolutionarily conserved cisregulatory elements that coordinate with other cis-elements to regulate spatiotemporal expression of Nolz-1 in different tissue organs during mouse embryogenesis
Summary
Nolz-1, the Drosophila nocA like zinc-finger gene-1 ( know as Znf503 or Zfp503 by Genome Informatics), is a member of the SP1-related nocA/elb/tlp-1 (NET) family. Members of the NET family include Nolz-1 and Znf703/Zfp703 in mammals, nlz and nlz in Danio rerio (zebrafish), nocA and elbow (elB) in Drosophila melanogaster (fruit fly) and tlp-1 gene in Caenorhabditis elegans (nematode worm) [1]. Mis-expression and ectopic expression of nlz genes cause abnormal rhombomere identities that implicate important roles of nlz genes in early hindbrain development [9,10,11]. Both nlz and nlz are involved in directing proper closure of the optic fissure, and play crucial roles for zebrafish eye development [12]
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