Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis.

Nature Neuroscience
Milan JoksimovicRajeshwar Awatramani

Abstract

The floor plate, an essential ventral midline organizing center that produces the morphogen Shh, has distinct properties along the neuraxis. The neurogenic potential of the floor plate and its underlying mechanisms remain unknown. Using Shh as a driver for lineage analysis, we found that the mouse midbrain, but not the hindbrain, floor plate is neurogenic, giving rise to dopamine (DA) neurons. Distinct spatiotemporal Shh and Wnt expression may distinguish the neurogenetic potential of these structures. We discovered an inhibitory role for Shh: removal of Shh resulted in neurogenesis from the hindbrain midline and, conversely, high doses of Shh inhibited proliferation and DA neuron production in midbrain cultures. We found that Wnt/beta-catenin signaling is necessary and sufficient for antagonizing Shh, DA progenitor marker induction and promotion of dopaminergic neurogenesis. These findings demonstrate how the dynamic interplay of canonical Wnt/beta-catenin signaling and Shh may orchestrate floor plate neurogenesis or a lack thereof.

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Citations

Dec 21, 2012·Journal of Molecular Neuroscience : MN·Einat Nissim-ElirazNissim Ben-Arie
Apr 7, 2010·Cell Stem Cell·Christopher A FasanoLorenz Studer
Oct 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Milan JoksimovicRajeshwar Awatramani
May 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sangmi ChungKwang-Soo Kim
May 18, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nicole GennetMeng Li
Jan 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Emma R AnderssonErnest Arenas
Dec 19, 2009·The Journal of Biological Chemistry·Kyle M SousaErnest Arenas
Jul 21, 2011·BMC Biology·Lia Panman, Thomas Perlmann
May 17, 2011·Neural Development·Maria T M Alves dos Santos, Marten P Smidt
Jan 24, 2012·Neural Development·Gonzalo Alvarez-BoladoSandra Blaess
Sep 2, 2011·Development·Cui-Ping YangSteven G Kernie
Jul 9, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mianzhi TangEric J Huang
Jun 4, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Beth YunRajeshwar Awatramani
Dec 18, 2013·Journal of Molecular Cell Biology·Clare L Parish, Lachlan H Thompson
Nov 30, 2013·Journal of Molecular Cell Biology·Milan Joksimovic, Rajeshwar Awatramani
Aug 26, 2014·Database : the Journal of Biological Databases and Curation·Michaela MatthesDietrich Trümbach
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