Congratulations to Caitlin!!! Her manuscript has been accepted at the Journal of Neuroscience! It's the culmination of a LOT of hard work over the last 4+ years, and she should be very proud of it! Thanks to Santiago and Brett for their work on the paper. A special thank you to our collaborators Odessa Yabut, Hector Gomez and Sam Pleasure from the Pleasure Lab at UCSF for a great collaboration.
The Dorsal Wave of Neocortical Oligodendrogenesis Begins Embryonically and Requires Multiple Sources of Sonic Hedgehog
Neural progenitor cells in the developing dorsal forebrain give rise to excitatory neurons, astrocytes and oligodendrocytes for the neocortex. Compared to neurons and astrocytes, less is known about the molecular mechanisms that instruct dorsal forebrain progenitors to an oligodendrocyte fate. In this study, we show that Sonic hedgehog (Shh) signaling is required in dorsal progenitors for their late embryonic transition to oligodendrogenesis. Using genetic lineage-tracing in mice of both sexes, we demonstrate that the majority of oligodendrocytes in the embryonic neocortex derive from Emx1+ dorsal forebrain progenitors. Deletion of the Shh signaling effector, Smo, specifically in Emx1+ progenitors led to significantly decreased oligodendrocyte numbers in the embryonic neocortex. Conversely, knockout of the Shh antagonist, Sufu, was sufficient to increase neocortical oligodendrogenesis.Using conditional knockout strategies, we found that Shh ligand is supplied to dorsal progenitors through multiple sources. Loss of Shh from Dlx5/6+ interneurons caused a significant reduction in oligodendrocytes in the embryonic neocortex. This phenotype was identical to that observed upon Shh deletion from the entire CNS using Nestin-Cre, indicating that interneurons migrating into the neocortex from the subpallium are the primary neural source of Shh for dorsal oligodendrogenesis. Additionally, deletion of Shh from migrating interneurons together with the choroid plexus epithelium led to a more severe loss of oligodendrocytes, suggesting that the choroid plexus is an important non-neural source of Shh ligand. Together, our studies demonstrate that the dorsal wave of neocortical oligodendrogenesis occurs earlier than previously appreciated, and requires highly regulated Shh signaling from multiple embryonic sources.
The lab was awarded a 1-year Grand Challenges Grant from the Linda Crnic Institute for Down Syndrome. The title of the grant is: "Defects in Neurogenesis and Neuronal Migration in DS Mouse Models: Elucidating the Developmental and Molecular Mechanisms."
Caitlin attended the Cold Spring Harbor Laboratory conference on Glia in Health and Disease. She presented her research in a poster titled "Activation of a ventral pathway in dorsal forebrain progenitors initiates cortical oligodendrogenesis."
Welcome to our newest lab member, Mark Gutierrez! Mark is a second-year student in the Cell Biology, Stem Cells and Development graduate program.
Caitlin, Brett and Santos attended the Society for Developmental Biology Annual Meeting in Snowbird, UT. Caitlin and Brett presented a poster on a new genetic tool being developed in the lab. We hung out with the marmots (not a typo) and potguts (also not a typo), and saw a raccoon family go fishing the garbage can. We also saw a Christian Bale painting at the SLC Temple Square. We may or may not have locked ourselves out of our condo and had to eat lunch in the street. Click here to learn more.
Santos received a 3-year Webb-Waring Biomedical Research Grant from the Boettcher Foundation, for his proposal on Brain Stem Cells in Development and Disease.
We got our first grant! Santos received a 1-year pilot grant from the Center for NeuroScience (CNS) and Colorado Clinical and Translational Sciences Institute (CCTSI). The title of the grant is: "Novel interactors of the Reelin signaling pathway and their potential roles in healthy brain function and Alzheimer's disease pathology."
Santos and Caitlin attended the Gordon Conference on Neural Development in Newport, RI. Caitlin presented her first poster from the Franco lab! We may or may not have skipped a session to watch Guardians of the Galaxy at the movie theater. We also may or may not have spent some time in the ER getting stitches after a happy hour "incident." Click here to learn more.
Santos presented a poster at the Society for Developmental Biology Annual Meeting in Seattle, WA.
We have our first graduate students! Our PRA Caitlin Winkler is now our CSD graduate student Caitlin Winkler. Fellow CSD classmate Santiago Fregoso will also join our lab as a graduate student.