Genetic dissection of the glutamatergic neuron system in cerebral cortex

Katherine S. Matho, Dhananjay Huilgol, William Galbavy, Miao He, Gukhan Kim, Xu An, Jiangteng Lu, Priscilla Wu, Daniela J. Bella, Ashwin S. Shetty, Ramesh Palaniswamy, Joshua Hatfield, Ricardo Raudales, Arun Narasimhan, Eric Gamache, Jesse M. Levine, Jason Tucciarone, Eric Szelenyi, Julie A. Harris, Partha P. Mitra, Pavel Osten, Paola Arlotta and Z. Josh Huang ()
Additional contact information
Katherine S. Matho: Cold Spring Harbor
Dhananjay Huilgol: Cold Spring Harbor
William Galbavy: Cold Spring Harbor
Miao He: Cold Spring Harbor
Gukhan Kim: Cold Spring Harbor
Xu An: Cold Spring Harbor
Jiangteng Lu: Cold Spring Harbor
Priscilla Wu: Cold Spring Harbor
Daniela J. Bella: Harvard University
Ashwin S. Shetty: Harvard University
Ramesh Palaniswamy: Cold Spring Harbor
Joshua Hatfield: Cold Spring Harbor
Ricardo Raudales: Cold Spring Harbor
Arun Narasimhan: Cold Spring Harbor
Eric Gamache: Cold Spring Harbor
Jesse M. Levine: Cold Spring Harbor
Jason Tucciarone: Cold Spring Harbor
Eric Szelenyi: Cold Spring Harbor
Julie A. Harris: Stony Brook University
Partha P. Mitra: Cold Spring Harbor
Pavel Osten: Cold Spring Harbor
Paola Arlotta: Harvard University
Z. Josh Huang: Cold Spring Harbor

Nature, 2021, vol. 598, issue 7879, 182-187

Abstract: Abstract Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels.

Date: 2021
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DOI: 10.1038/s41586-021-03955-9

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