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XB-ART-44950
Development April 1, 2012; 139 (8): 1487-97.

A hindbrain-repressive Wnt3a/Meis3/Tsh1 circuit promotes neuronal differentiation and coordinates tissue maturation.

Elkouby YM , Polevoy H , Gutkovich YE , Michaelov A , Frank D .


Abstract
During development, early inducing programs must later be counterbalanced for coordinated tissue maturation. In Xenopus laevis embryos, activation of the Meis3 transcription factor by a mesodermal Wnt3a signal lies at the core of the hindbrain developmental program. We now identify a hindbrain restricting circuit, surprisingly comprising the hindbrain inducers Wnt3a and Meis3, and Tsh1 protein. Functional and biochemical analyses show that upon Tsh1 induction by strong Wnt3a/Meis3 feedback loop activity, the Meis3-Tsh1 transcription complex represses the Meis3 promoter, allowing cell cycle exit and neuron differentiation. Meis3 protein exhibits a conserved dual-role in hindbrain development, both inducing neural progenitors and maintaining their proliferative state. In this regulatory circuit, the Tsh1 co-repressor controls transcription factor gene expression that modulates cell cycle exit, morphogenesis and differentiation, thus coordinating neural tissue maturation. This newly identified Wnt/Meis/Tsh circuit could play an important role in diverse developmental and disease processes.

PubMed ID: 22399680
Article link: Development

Genes referenced: acss2.2 cdknx cyp26a1 dkk1 egr2 en2 epha2 gal.2 hoxb9 irx3 meis3 myc myl2 nog odc1 snai2 sox3 tshb tshz1 tub tubb2b wnt3 wnt3a
Morpholinos: meis3 MO1 tshz1 MO1 wnt3a MO1 wnt3a MO2 wnt3a MO3


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