COUP-TFIIis essential for radial and anteroposterior patterning of the stomach

Abstract

COUP-TFII, an orphan member of the steroid receptor superfamily,has been implicated in mesenchymal-epithelial interaction during organogenesis. The generation of a lacZ knock-in allele in the COUP-TFII locus in mice allows us to use X-gal staining to follow the expression of COUP-TFII in the developing stomach. We found COUP-TFII is expressed in the mesenchyme and the epithelium of the developing stomach. Conditional ablation of floxed COUP-TFII by Nkx3-2Cre recombinase in the gastric mesenchyme results in dysmorphogenesis of the developing stomach manifested by major patterning defects in posteriorization and radial patterning. The epithelial outgrowth,the expansion of the circular smooth muscle layer and enteric neurons as well as the posteriorization of the stomach resemble phenotypes exhibited by inhibition of hedgehog signaling pathways. Using organ cultures and cyclopamine treatment, we showed downregulation of COUP-TFII level in the stomach, suggesting COUP-TFII as a target of hedgehog signaling in the stomach. Our results are consistent with a functional link between hedgehog proteins and COUP-TFII, factors that are vital for epithelial-mesenchymal interactions.

The expression pattern of nuclear receptors during cerebellar development

“…In general, COUP-TFI is more highly expressed in the neuronal tissue of the central and peripheral nervous systems, whereas COUP-TFII is expressed in the mesenchyme of developing organs (Pereira et al, 1995). Loss of function assays indicate that COUP-TFI is important for neurogenesis and neural crest cell differentiation during embryonic development Zhou et al, 2001;Yamaguchi et al, 2004), while COUP-TFII acts as a major regulator of angiogenesis, vein identity, and organ development (Pereira et al, 1999;Takamoto et al, 2005;You et al, 2005). In the cerebellum, the expressions patterns of these two receptors are not co-localized.…”

“…Unlike COUP-TFI, COUP-TFII is highly expressed only in the anterior half of the cerebellum in a manner similar to that of Sonic hedgehog (Shh), which is important for cerebellar foliation (Corrales et al, 2004(Corrales et al, , 2006. Since COUP-TFII is more likely to be a downstream target of Shh signaling (Krishnan et al, 1997;Takamoto et al, 2005), it is reasonable to expect that COUP-TFII may play an important role in cerebellar development. Additionally, when one considers the temporal expression pattern of COUP-TFI and ERR␥, it is probable that they may also function during cerebellar development.…”

Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos

“…The methods for generating Prox1 ϩ/LacZ , COUP-TFII flox/flox , and Prox1 ϩ/GFPCre mice were previoulsy reported. 4,10,11 PlexinD1 Ϫ/Ϫ embryos were previously described. 12 All of the mouse experiments were approved by the St Jude Children's Research Hospital Animal Care and Use Committee.…”

Orphan Nuclear Receptor Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) Protein Negatively Regulates Bone Morphogenetic Protein 2-induced Osteoblast Differentiation through Suppressing Runt-related Gene 2 (Runx2) Activity

“…COUP-TFII-deficient mice die in utero with defects in heart development and angiogenesis. Tissue-specific knock-out studies have shown that COUP-TFII is required for the development of limb, skeletal muscles, and stomach and plays a critical role in determining vein identity (11,13,14). Even though the ligands of COUP-TFII are still unknown, the roles of COUP-TFII during angiogenesis, female reproduction, and neurogenesis have been well established.…”