Yaniv M Elkouby, Hanna Polevoy, Yoni E Gutkovich, Ariel Michaelov, Dale Frank
Department of Biochemistry, The Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Development (Cambridge, England) 2012 AprDuring 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.
Yaniv M Elkouby, Hanna Polevoy, Yoni E Gutkovich, Ariel Michaelov, Dale Frank. A hindbrain-repressive Wnt3a/Meis3/Tsh1 circuit promotes neuronal differentiation and coordinates tissue maturation. Development (Cambridge, England). 2012 Apr;139(8):1487-97
PMID: 22399680
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