Identification of a Novel Sonic Hedgehog Response Element in the Chicken Ovalbumin Upstream Promoter-Transcription Factor II Promoter

Krishnan, Venkatesh; Elberg, Gerard; Tsai, Ming‐Jer; Tsai, Sophia Y.

doi:10.1210/mend.11.10.9992

Cited by 51 publications

(21 citation statements)

References 33 publications

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“…The expression patterns in the zymogenic unit resemble that of Shh (van den Brink et al, 2001). Taken together of the above findings, we speculate that Shh might regulate COUP-TFII in the stomach in a similar manner as previously shown in the motoneurons (Krishnan et al, 1997a).…”

Section: Discussionsupporting

confidence: 83%

“…In the developing neural tube, Shh has been shown to regulate COUP-TFII expression during the differentiation of motoneurons (Lutz et al, 1994). We have also identified a 5′-regulatory element that mediates Shh stimulation of COUP-TFII expression (Krishnan et al, 1997a;Krishnan et al, 1997b). COUP-TFII is likely to be a downstream target of Shh signaling, and the requirement for Shh in gastric organogenesis led us to infer that COUP-TFII may play a role in stomach development.…”

Section: Introductionmentioning

confidence: 86%

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

et al. 2005

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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.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 86%

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

et al. 2005

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“…Several reports have suggested Gli-independent mechanisms of Shh signaling in vertebrates (Krishnan et al, 1997a;Krishnan et al, 1997b;Lewis et al, 1999). However, our analysis of Gli function has unequivocally demonstrated a requirement for Gli2 and Gli3 in mediating Shh-induced sclerotomal gene expression.…”

Section: Discussionmentioning

confidence: 99%

Interplays of Gli2 and Gli3 and their requirement in mediating Shh-dependent sclerotome induction

et al. 2003

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Sonic hedgehog (Shh) signaling is essential for sclerotome development in the mouse. Gli2 and Gli3 are thought to be the primary transcriptional mediators of Shh signaling; however, their roles in Shh induction of sclerotomal genes have not been investigated. Using a combination of mutant analysis and in vitro explant assays, we demonstrate that Gli2 and Gli3 are required for Shh-dependent sclerotome induction. Gli2–/–Gli3–/–embryos exhibit a severe loss of sclerotomal gene expression, and somitic mesoderm from these embryos cannot activate sclerotomal genes in response to exogenous Shh. We find that one copy of either Gli2 or Gli3is required to mediate Shh induction of sclerotomal markers Pax1 and Pax9 in vivo and in vitro. Although Gli2 is generally considered an activator and Gli3 a repressor, our results also reveal a repressor function for Gli2 and an activator function for Gli3 in the developing somite. To further dissect the function of each Gli, we used adenovirus to overexpress Gli1, Gli2 and Gli3 in presomitic mesoderm explants. We find that each Gli preferentially activates a distinct set of Shh target genes, suggesting that the functions of Shh in patterning,growth and negative feedback are divided preferentially between different Gli proteins in the somite.

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“…Binding between Hh and PTCH results in de-repression of SMO, thereby activating a cascade that leads to the translocation of the active form of the transcription factor GLI to the nucleus. Nuclear GLI activates expression of a variety of target genes such as BMP4, FOXA2, ISL1, and FOXM1 (Krishnan et al, 1997; Van den Brink et al, 2001;Teh et al, 2002). Recently, Ihog (interference Hh) and Boi, which de-repress SMO through interaction with Hh ligands, have been identified in Drosophila (Yao et al, 2006).…”

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confidence: 99%

Cross talk between hedgehog and epithelial–mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers

Ohta

Aoyagi²,

Fukaya³

et al. 2008

Br J Cancer

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We previously reported hedgehog (Hh) signal activation in the mucus-secreting pit cell of the stomach and in diffuse-type gastric cancer (GC). Epithelial -mesenchymal transition (EMT) is known to be involved in tumour malignancy. However, little is known about whether and how both signallings cooperatively act in diffuse-type GC. By microarray and reverse transcription -PCR, we investigated the expression of those Hh and EMT signalling molecules in pit cells and in diffuse-type GCs. How both signallings act cooperatively in those cells was also investigated by the treatment of an Hh-signal inhibitor and siRNAs of Hh and EMT transcriptional key regulator genes on a mouse primary culture and on human GC cell lines. Pit cells and diffuse-type GCs co-expressed many Hh and EMT signalling genes. Mesenchymal-related genes (WNT5A, CDH2, PDGFRB, EDNRA, ROBO1, ROR2, and MEF2C) were found to be activated by an EMT regulator, SIP1/ZFHX1B/ZEB2, which was a target of a primary transcriptional regulator GLI1 in Hh signal. Furthermore, we identified two cancer-specific Hh targets, ELK1 and MSX2, which have an essential role in GC cell growth. These findings suggest that the gastric pit cell exhibits mesenchymal-like gene expression, and that diffuse-type GC maintains expression through the Hh -EMT pathway. Our proposed extensive Hh -EMT signal pathway has the potential to an understanding of diffusetype GC and to the development of new drugs.

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Identification of a Novel Sonic Hedgehog Response Element in the Chicken Ovalbumin Upstream Promoter-Transcription Factor II Promoter

Cited by 51 publications

References 33 publications

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

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

Interplays of Gli2 and Gli3 and their requirement in mediating Shh-dependent sclerotome induction

Cross talk between hedgehog and epithelial–mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers

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