Genetic dissection of the glutamatergic neuron system in cerebral cortex.

Matho, Katherine S, Huilgol, Dhananjay, Galbavy, William, He, Miao, Kim, Gukhan, An, Xu, Lu, Jiangteng, Wu, Priscilla, Di Bella, Daniela J, Shetty, Ashwin S, Palaniswamy, Ramesh, Hatfield, Joshua, Raudales, Ricardo, Narasimhan, Arun, Gamache, Eric, Levine, Jesse M, Tucciarone, Jason, Szelenyi, Eric, Harris, Julie A, Mitra, Partha P, Osten, Pavel, Arlotta, Paola, Huang, Z Josh (October 2021) Genetic dissection of the glutamatergic neuron system in cerebral cortex. Nature, 598 (7879). pp. 182-187. ISSN 0028-0836

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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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organs, tissues, organelles, cell types and functions > tissues types and functions > cerebral cortex bioinformatics > genomics and proteomics > small molecules > Glutamate organism description > animal > mammal organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > pyramidal neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > pyramidal neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > pyramidal neurons organism description > animal > mammal > rodent bioinformatics > genomics and proteomics > small molecules bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Matho, Katherine Huilgol, Dhananjay Galbavy, William He, Miao Lu, Jiangteng Wu, Priscilla Palaniswamy, Ramesh Raudales, Ricardo Narasimhan, Arun Levine, Jesse Tucciarone, Jason Szelenyi, Eric Mitra, Partha P. Osten, Pavel Kim, Gukhan An, Xu Hatfield, Joshua Gamache, Eric Huang, Z. Josh
Communities:	CSHL labs > Huang lab CSHL labs > Mitra lab CSHL labs > Osten lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	6 October 2021
Date Deposited:	13 Oct 2021 15:15
Last Modified:	25 Jan 2024 15:18
PMCID:	PMC8494647
URI:	https://repository.cshl.edu/id/eprint/40385

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