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Publication : β-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus.

First Author  Bluske KK Year  2012
Journal  Development Volume  139
Issue  15 Pages  2692-702
PubMed ID  22745311 Mgi Jnum  J:185651
Mgi Id  MGI:5429623 Doi  10.1242/dev.072314
Citation  Bluske KK, et al. (2012) beta-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus. Development 139(15):2692-702
abstractText  Neural progenitor cells within the developing thalamus are spatially organized into distinct populations. Their correct specification is critical for generating appropriate neuronal subtypes in specific locations during development. Secreted signaling molecules, such as sonic hedgehog (Shh) and Wnts, are required for the initial formation of the thalamic primordium. Once thalamic identity is established and neurogenesis is initiated, Shh regulates the positional identity of thalamic progenitor cells. Although Wnt/beta-catenin signaling also has differential activity within the thalamus during this stage of development, its significance has not been directly addressed. In this study, we used conditional gene manipulations in mice and explored the roles of beta-catenin signaling in the regional identity of thalamic progenitor cells. We found beta-catenin is required during thalamic neurogenesis to maintain thalamic fate while suppressing prethalamic fate, demonstrating that regulation of regional fate continues to require extrinsic signals. These roles of beta-catenin appeared to be mediated at least partly by regulating two basic helix-loop-helix (bHLH) transcription factors, Neurog1 and Neurog2. beta-Catenin and Shh signaling function in parallel to specify two progenitor domains within the thalamus, where individual transcription factors expressed in each progenitor domain were regulated differently by the two signaling pathways. We conclude that beta-catenin has multiple functions during thalamic neurogenesis and that both Shh and beta-catenin pathways are important for specifying distinct types of thalamic progenitor cells, ensuring that the appropriate neuronal subtypes are generated in the correct locations.
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