The cerebral cortex comprises a vast number of glutamatergic pyramidal neurons (PyNs) and GABAergic interneurons that are organized into a layered structure and form a constellation of functional areas. With their large dendrites and long axons, PyNs consist of diverse types that constitute the scaffolds of local circuits, mediate myriad inter-areal processing streams, and underlie all cortical output channels. The developmental genetic mechanisms that give rise to distinct PyN types are not well understood. All PyNs are generated by embryonic radial glial progenitors (RGs) from the embryonic dorsal telencephalon either directly or by indirect neurogenesis via intermediate progenitors (IPs). However, the contributions of these two types of principal progenitors and neurogenic mechanisms to the diversification and amplification of PyNs are unknown. Using a suite of mouse genetic tools that allow differential fate mapping of RGs and IPs and labeling of their PyN progenies, we found that direct and indirect neurogenesis make substantially different contributions to PyN types, such as corticofugal and cortico-striatal neurons. These results suggest that IPs and indirect neurogenesis have evolved to diversify PyN types as well as amplify PyN numbers.
Classic embryonic cell birth-dating studies revealed an inside-out trend of cortical lamination, but the progenitor and lineage mechanisms, and the role IPs in particular, in the generation of PyN projection types are unclear. Using an inducible Tbr2-CreER mouse driver line, we performed comprehensive fate mapping of IPs throughout neurogenesis. In addition to quantifying the laminar location of fate-mapped PyNs, we combined anterograde and retrograde viral labeling to reveal their axon projection patterns. We found that 1) individual IPs appear fate-committed to produce “twin” PyNs with near identical locations and morphologies, 2) upper and lower layer PyNs are generated together at both early and late embryonic times, 3) non-consecutive layers are generated at the same time, and 4) the same layer can be generated at different times. Together with the analysis of axon projection patterns of fate-mapped PyNs, these results reveal that the basis underlying the construction of cortical architecture follows an orderly production and deployment of PyN projection types rather than a strict inside-out sequence.
|Advisor:||Huang, Josh, Shelly, Maya|
|Commitee:||Koulakov, Alexei, Osten, Pavel, Shi, Songhai|
|School:||State University of New York at Stony Brook|
|School Location:||United States -- New York|
|Source:||DAI-B 79/12(E), Dissertation Abstracts International|
|Keywords:||Intermediate progenitor, Pyramidal neuron, TBR2|
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