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Genetic dissection of the glutamatergic neuron system in cerebral cortex

Author

Listed:
  • Katherine S. Matho

    (Cold Spring Harbor)

  • Dhananjay Huilgol

    (Cold Spring Harbor
    Duke University Medical Center)

  • William Galbavy

    (Cold Spring Harbor
    Stony Brook University)

  • Miao He

    (Cold Spring Harbor
    Fudan University)

  • Gukhan Kim

    (Cold Spring Harbor)

  • Xu An

    (Cold Spring Harbor
    Duke University Medical Center)

  • Jiangteng Lu

    (Cold Spring Harbor
    Shanghai Jiaotong University Medical School)

  • 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
    Duke University Medical Center)

  • Ricardo Raudales

    (Cold Spring Harbor
    Stony Brook University)

  • Arun Narasimhan

    (Cold Spring Harbor)

  • Eric Gamache

    (Cold Spring Harbor)

  • Jesse M. Levine

    (Cold Spring Harbor
    Stony Brook University)

  • Jason Tucciarone

    (Cold Spring Harbor
    Stony Brook University
    Stanford University School of Medicine)

  • Eric Szelenyi

    (Cold Spring Harbor)

  • Julie A. Harris

    (Stony Brook University
    Allen Institute for Brain Science)

  • Partha P. Mitra

    (Cold Spring Harbor)

  • Pavel Osten

    (Cold Spring Harbor)

  • Paola Arlotta

    (Harvard University
    Broad Institute of MIT and Harvard)

  • Z. Josh Huang

    (Cold Spring Harbor
    Duke University Medical Center)

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.

Suggested Citation

  • 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 & Ric, 2021. "Genetic dissection of the glutamatergic neuron system in cerebral cortex," Nature, Nature, vol. 598(7879), pages 182-187, October.
  • Handle: RePEc:nat:nature:v:598:y:2021:i:7879:d:10.1038_s41586-021-03955-9
    DOI: 10.1038/s41586-021-03955-9
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    Cited by:

    1. Yanmei Liu & Jiahe Zhang & Zhishan Jiang & Meiling Qin & Min Xu & Siyu Zhang & Guofen Ma, 2024. "Organization of corticocortical and thalamocortical top-down inputs in the primary visual cortex," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Fae N. Kronman & Josephine K. Liwang & Rebecca Betty & Daniel J. Vanselow & Yuan-Ting Wu & Nicholas J. Tustison & Ashwin Bhandiwad & Steffy B. Manjila & Jennifer A. Minteer & Donghui Shin & Choong Heo, 2024. "Developmental mouse brain common coordinate framework," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Jia-Ru Wei & Zhao-Zhe Hao & Chuan Xu & Mengyao Huang & Lei Tang & Nana Xu & Ruifeng Liu & Yuhui Shen & Sarah A. Teichmann & Zhichao Miao & Sheng Liu, 2022. "Identification of visual cortex cell types and species differences using single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    4. Arpiar Saunders & Kee Wui Huang & Cassandra Vondrak & Christina Hughes & Karina Smolyar & Harsha Sen & Adrienne C. Philson & James Nemesh & Alec Wysoker & Seva Kashin & Bernardo L. Sabatini & Steven A, 2022. "Ascertaining cells’ synaptic connections and RNA expression simultaneously with barcoded rabies virus libraries," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    5. Qingtao Sun & Jianping Zhang & Anan Li & Mei Yao & Guangcai Liu & Siqi Chen & Yue Luo & Zhi Wang & Hui Gong & Xiangning Li & Qingming Luo, 2022. "Acetylcholine deficiency disrupts extratelencephalic projection neurons in the prefrontal cortex in a mouse model of Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-22, December.

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