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Dev Biol 2011 Mar 15;3512:297-310. doi: 10.1016/j.ydbio.2010.11.037.
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A gene regulatory network controlling hhex transcription in the anterior endoderm of the organizer.

Rankin SA , Kormish J , Kofron M , Jegga A , Zorn AM .

The homeobox gene hhex is one of the earliest markers of the anterior endoderm, which gives rise to foregut organs such as the liver, ventral pancreas, thyroid, and lungs. The regulatory networks controlling hhex transcription are poorly understood. In an extensive cis-regulatory analysis of the Xenopus hhex promoter, we determined how the Nodal, Wnt, and BMP pathways and their downstream transcription factors regulate hhex expression in the gastrula organizer. We show that Nodal signaling, present throughout the endoderm, directly activates hhex transcription via FoxH1/Smad2 binding sites in the proximal -0.44 Kb promoter. This positive action of Nodal is suppressed in the ventral-posterior endoderm by Vent 1 and Vent2, homeodomain repressors that are induced by BMP signaling. Maternal Wnt/β-catenin on the dorsal side of the embryo cooperates with Nodal and indirectly activates hhex expression via the homeodomain activators Siamois and Twin. Siamois/Twin stimulate hhex transcription through two mechanisms: (1) they induce the expression of Otx2 and Lim1 and together Siamois, Twin, Otx2, and Lim1 appear to promote hhex transcription through homeobox sites in a Wnt-responsive element located between -0.65 to -0.55 Kb of the hhex promoter. (2) Siamois/Twin also induce the expression of the BMP-antagonists Chordin and Noggin, which are required to exclude Vents from the organizer allowing hhex transcription. This study reveals a complex network regulating anterior endoderm transcription in the early embryo.

PubMed ID: 21215263
PMC ID: PMC3044432
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cer1 chrd ctnnb1 foxh1.2 gsc hhex lhx1 mix1 myc myl7 nodal nodal1 nodal3.1 nodal3.2 nog otx2 prl.2 sia1 sia2 smad2 tbx2 tcf3 tcf7l1 ventx1.2 ventx2.2 wnt8a
Morpholinos: chrd.1 MO1 chrd.1 MO2 ctnnb1 MO1 gsc MO1 lhx1 MO1 nog MO1 otx2 MO1 sia1 MO1 sia2 MO1 smad2 MO1 smad2 MO2 tcf7l1 MO2 ventx1.1 MO1 ventx2.1 MO2

Phenotypes: Xla Wt + Activin + CHX + animal cap explant (fig.2.c) [+]

Article Images: [+] show captions
References [+] :
Ahmed, Early endodermal expression of the Xenopus Endodermin gene is driven by regulatory sequences containing essential Sox protein-binding elements. 2004, Pubmed, Xenbase