Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis

Authors:
  • BYBeth A Yun
    Beth A Yun
  • RKRaja Kittappa
    Raja Kittappa
  • AAAngela M Anderegg
    Angela M Anderegg
  • WCWendy W Chang
    Wendy W Chang
  • MTMakoto M Taketo
    Makoto M Taketo
  • RMRonald D G McKay
    Ronald D G McKay
  • RARajeshwar B Awatramani
    Rajeshwar B Awatramani
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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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