Samuel Pleasure, MD, PhD
Samuel Pleasure, MD, PhD
Control of neural stem cell fate and migration by developmental mediators
We have several ongoing projects related to the developmental control of neural stem cell behavior.
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.
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.
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.
Zhou CJ, Pinson KI, and Pleasure SJ. (2004) Severe defects in dorsal thalamic development in LRP6 mutants. Journal of Neuroscience 24:7632-7639.
Zhao C, Avilés C, Abel RA, Almli CR, McQuillen P, Pleasure SJ. (2005) Hippocampal and visuospatial learning defects in mice with deletion of Frizzled9, a gene in the Williams syndrome deletion interval. Development 132:2917-2927.
Pozniak CD and Pleasure SJ. (2006) A Tale of Two Signals: Wnt and Hedgehog in Dentate Neurogenesis. Science STKE 2006:pe5.
Paredes MF, Li G, Berger O, Baraban SC, Pleasure SJ. (2006) Stromal-derived factor-1 (CXCL12) regulates laminar position of Cajal-Retzius cells in normal and dysplastic brains. J Neurosci 26(37):9404-12.