Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis (Nat Neurosci, 2009, 12:125-131)

報告日期: 2009/05/01
報告時間: 17:10/18:00
報告學生: 洪惠琪
講評老師: 簡伯武


Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis

Native Neuroscience, 12,125-132, 2009

Milan Joksimovic1, Beth A Yun1, Raja Kittappa, Angela M Anderegg, Wendy WC hang, Makoto M Taketo, Ronald D G McKay & Rajeshwar B Awatramani


Commentator: Gean, Po-Wu, Ph.D.

Speaker: Hung, Huei-Chi

17:010-18:00, May 1, 2009, Room 602



   The neural tube floor plate, an essential embryonic CNS ventral midline organizing center that produces the morphogen Sonic hedgehog (Shh) signal, has distinct properties along the neuraxis. The floor plate is composed of ependymal cells and was thought to be unable to differentiate into neurons. But, the view of the Shh-positive midbrain floor plate cells give rise to midbrain DA neurons. As yet, little was known about the neurogenic potential of the floor plate and its underlying mechanisms. The authors demonstrate that the mouse midbrain, floor plate was neurogenic, giving rise to dopamine (DA) neurons. Distinct spatiotemporal Shh and Wnt expression may distinguish the neurogenetic potential of these structures. 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. Finally, the authors found that Wnt/beta-catenin signaling was necessary and sufficient for antagonizing Shh, DA progenitor marker induction and promotion of dopaminergic neurogenesis from the floor plate. Present studies show the new light on the molecular underpinnings of DA neurogenesis and will be important for programming stem cells to DA neurons, an important goal of stem cell–based approaches toward understanding and treating Parkinson’s disease.



1. Placzek, M. & Briscoe, J. The floor plate: multiple cells, multiple signals. Nat. Rev. Neurosci. 6, 230–240 (2005).

2. Kittappa, R., Chang,W.W., Awatramani, R.B. & McKay, R.D. The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age. PLoS Biol. 5, e325 (2007).