Genetic dissection of the glutamatergic neuron system in cerebral cortex.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Matho, KS; Huilgol, D; Galbavy, W; He, M; Kim, G; An, X; Lu, J; Wu, P; Di Bella, DJ; Shetty, AS; Palaniswamy, R; Hatfield, J; Raudales, R; Narasimhan, A; Gamache, E; Levine, JM; Tucciarone, J; Szelenyi, E; Harris, JA; Mitra, PP; Osten, P; Arlotta, P; Huang, ZJ

Published Date

  • October 2021

Published In

Volume / Issue

  • 598 / 7879

Start / End Page

  • 182 - 187

PubMed ID

  • 34616069

Pubmed Central ID

  • PMC8494647

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/s41586-021-03955-9

Language

  • eng

Conference Location

  • England