Article abstract
Nature Neuroscience 12, 125 - 131 (2009)
Published online: 4 January 2009 | doi:10.1038/nn.2243
Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis
Milan Joksimovic1, Beth A Yun1, Raja Kittappa2, Angela M Anderegg1, Wendy W Chang2, Makoto M Taketo3, Ronald D G McKay2 & Rajeshwar B Awatramani1
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.
- Northwestern University Feinberg Medical School, Department of Neurology and Center for Genetic Medicine, 7-113 Lurie Bldg, 303 E Superior Street, Chicago, Illinois 60611, USA.
- Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, Porter Neuroscience Research Center, Building 35, Room 3A-201, 35 Convent Drive, MSC 3703, Bethesda, Maryland 20892-4157, USA.
- Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo, Kyoto 606-8501, Japan.
Correspondence to: Rajeshwar B Awatramani1 e-mail: r-awatramani@northwestern.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Too much Sonic, too few neuronsNature Neuroscience News and Views (01 Feb 2009)
Recycling signaling molecules during developmentNature Neuroscience News and Views (01 Feb 2002)
RESEARCH
β-catenin?mediated Wnt signaling regulates neurogenesis in the ventral telencephalonNature Neuroscience Article (01 Dec 2008)
Transcriptional repression coordinates the temporal switch from motor to serotonergic neurogenesisNature Neuroscience Article (01 Nov 2007)
See all 55 matches for Research
