Neuroscience Graduate Program at UCSF
Control of Neural Stem Cell Fate and Migration in the Cortex
We have several ongoing projects related to the developmental control of neural stem cell behavior.
a) Development of the dentate gyrus neurogenic niche. The dentate gyrus is one of the few regions in the adult brain with ongoing production of neurons throughout the lifespan. Many recent studies demonstrate that this ongoing neurogenesis is under the control of molecular signaling pathways that also control the development of the dentate gyrus. The lab studies the roles of several developmental signaling systems (including Wnts, Shh, Tgfß and chemokines) in the specification, migration and persistence of neural stem cells in the dentate gyrus.
b) Meningeal-cortical interactions during development. Throughout development the cortex develops in close association with the pial meninges, a mesenchymal cell layer that produces the basement membrane for the developming cortex. In addition, to the known roles for the meninges in providing extracellular matrix for the cortex, the lab is studying the roles of the meninges in more actively regulating cortical development by the production of secreted signaling molecules that control proliferation, migration and survival of cortical neurons and oligodendrocytes.
c) Transcriptional control of neural stem cell fate. During development neural stem cell fate is regulated by the action of cascades of regulatory transcription factors. We are examining the functions and direct targets of transcription factors that directly regulate the decision whether to adopt neuronal or glial cell fates. In particular, we are studying the control of oligodendrocyte cell fate by members of the Sox family of transcription factors.
Please refer to research summary for information on current projects.
Youngshik Choe, Postdoctoral Fellow
Laura Cocas, Postdoctoral Fellow
Susan Harrison-Uy, Postdoctoral Fellow
Trung Huynh, Lab Manager
Gloria Fernandez Garcia, Research Specialist
Grant Li, Postdoctoral Fellow
Odessa Yabut, Postdoctoral Felow
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JA Siegenthaler, AM Ashique, K Zarbalis, KP Patterson, JH Hecht, MA Kane, AE Folias, Y Choe, SR May, T Kume, JL Napoli, AS Peterson, SJ Pleasure (2009) Retinoic acid from the meninges regulates cortical neuron generation. Cell 139:597-609.
JH Hecht, JA Siegenthaler, KP Patterson, SJ Pleasure (2010) Primary cellular meningeal defects cause neocortical dysplasia and dyslamination. Annals of Neurology 68:454-464.
AJ Langseth, RN Munji, Y Choe, T Huynh, CD Pozniak, SJ Pleasure (2010) Wnts regulate the timing and efficiency of OPC generation in the telencephalon. Journal of Neuroscience 30:13367-13372.
CD Pozniak, A Langseth, GJP Dijkgraaf, Y Choe, Z Werb, SJ Pleasure (2010) Sox10 directs neural stem cells toward the oligodendrocyte lineage by decreasing Suppressor of Fused expression. PNAS 107:21795-21800.
R Munji, Y Choe, G Li, J Siegenthaler, SJ Pleasure (2011) Wnt signaling regulates neuronal differentiation of cortical intermediate progenitors. Journal of Neuroscience 31:1676-1687.
Y Choe, JA Siegenthaler, SJ Pleasure (2012) A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation. Neuron 73:698-712.
K Zarbalis, Y Choe, JA Siegenthaler, SJ Pleasure (2012) Meningeal Defects alter the tangential migration of cortical interneurons in Foxc1hith/hith mice. Neural Development, 7:2.
SJ Harrison-Uy, JA Siegenthaler, A Faedo, JL Rubenstein, SJ Pleasure (2013) CoupTFI is required for retinoic acid mediated cortical development in Foxc1 mutant mice. PLoS ONE 8(3): e58219. doi:10.1371/journal.pone.0058219
Y Choe, A Kozlova, D Graf, SJ Pleasure (2013) Bone morphogenic protein signaling is a major determinant of dentate development. Journal of Neuroscience 33:6766-6775.
G Li, L Fang, G Fernandez, SJ Pleasure (2013) The ventral hippocampus is the embryonic origin for adult neural stem cells in the dentate gyrus. Neuron 78:657:672.
Sam Pleasure M.D./Ph.D.
Office Phone: 415-502-5683
Lab Phone: 415-514-4949
UCSF Mission Bay, Box 3206
Department of Neurology
675 Nelson Rising Lane, Room 214
San Francisco, CA 94158