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. 2021. Genetic dissection of the glutamatergic neuron system in cerebral cortex. Nature. 598(7879):182-187. Pubmed: 34616069 DOI:10.1038/s41586-021-03955-9


Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex, yet all derive from neural progenitors of the embryonic dorsal telencephalon. 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.
© 2021. The Author(s).

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Dr. Arlotta is interested in understanding the molecular laws that govern the birth, differentiation and assembly of the cerebral cortex, the part of the brain that controls how we sense, move and think. She integrates developmental and evolutionary knowledge to investigate therapies for brain repair and for modeling neuropsychiatric disease.

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