Dll1 is a Potential CDX2 Target Gene

Title: Dll1 is a Potential CDX2 Target Gene
Authors: Lam, Jennifer
Date: 2010
Abstract: The functional redundancy and peri-implantation lethality inherent to members of the CDX family has traditionally limited their investigation. As such, the development by our lab of a conditional null mutant, obliterating CDX activity in the mouse, has opened up an exploration of their additional roles. Along with the loss of caudal tissue and failure of neural tube closure, Cdx1/2 null mutants exhibit abnormal somites, an observation which is echoed by the misregulation of many somitic players including members of the Wnt and Notch signaling pathways upon microarray analysis. The replication of altered expression patterns in situ and identification of consensus CDX response elements (CDRE) in the proximal promoter regions validated many of these genes as potential CDX targets. Characterization of one candidate in particular, DIl1, revealed reduced expression in the absence of CDX and overlapping expression domains with CDX members as well as somitic anomalies in Dil1 null mutants. The identification of two highly conserved putative CDRE in the proximal promoter region, in addition to the ability of CDX2 to occupy the promoter in the vicinity of these sites in vivo and specifically bind the identified motifs in vitro, was consistent with direct regulation. Functional analysis of CDX2 in association with the Dll1 promoter has so far proven inconclusive, but synergistic induction of the wildtype promoter in the presence of TBX6 supports a potential co-regulation. Overall, this thesis presents evidence for delta-like 1(Dll1) as a potential direct target of CDX2. Moreover, these findings support the possibility that CDX may regulate players in the Notch and Wnt signaling pathways and thereby play an important role in somitogenesis.
URL: http://hdl.handle.net/10393/28896
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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