Journal
CELL REPORTS
Volume 16, Issue 1, Pages 92-105Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.05.072
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Funding
- National Institute of Child Health and Human Development [U54 HD083091]
- NIH [R01 NS085081, R01 NS092339]
- German Research Foundation (DFG) Emmy Noether Programme [AR732/1-1]
- Lejeune Foundation
- ProRett Italia
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Intermediate progenitors (IPs) amplify the production of pyramidal neurons, but their role in selective genesis of cortical layers or neuronal subtypes remains unclear. Using genetic lineage tracing in mice, we find that IPs destined to produce upper cortical layers first appear early in corticogenesis, by embryonic day 11.5. During later corticogenesis, IP laminar fates are progressively limited to upper layers. We examined the role of Tbr2, an IP-specific transcription factor, in laminar fate regulation using Tbr2 conditional mutant mice. Upon Tbr2 inactivation, fewer neurons were produced by immediate differentiation and laminar fates were shifted upward. Genesis of subventricular mitoses was, however, not reduced in the context of a Tbr2-null cortex. Instead, neuronal and laminar differentiation were disrupted and delayed. Our findings indicate that upper-layer genesis depends on IPs from many stages of corticogenesis and that Tbr2 regulates the tempo of laminar fate implementation for all cortical layers.
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