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Vision-dependent specification of cell types and function in the developing cortex

View ORCID ProfileSarah Cheng, View ORCID ProfileSalwan Butrus, View ORCID ProfileLiming Tan, Vincent Xu, View ORCID ProfileSrikant Sagireddy, View ORCID ProfileJoshua T. Trachtenberg, View ORCID ProfileKarthik Shekhar, View ORCID ProfileS. Lawrence Zipursky
doi: https://doi.org/10.1101/2021.08.10.455824
Sarah Cheng
1Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
2Department of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
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Salwan Butrus
3Department of Chemical and Biomolecular Engineering; Helen Wills Neuroscience Institute; California Institute for Quantitative Biosciences, QB3, University of California, Berkeley, CA, USA 94720
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Liming Tan
1Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
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Vincent Xu
1Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
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Srikant Sagireddy
3Department of Chemical and Biomolecular Engineering; Helen Wills Neuroscience Institute; California Institute for Quantitative Biosciences, QB3, University of California, Berkeley, CA, USA 94720
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Joshua T. Trachtenberg
4Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
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Karthik Shekhar
3Department of Chemical and Biomolecular Engineering; Helen Wills Neuroscience Institute; California Institute for Quantitative Biosciences, QB3, University of California, Berkeley, CA, USA 94720
5Faculty Scientist, Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, CA, USA 94720
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  • For correspondence: kshekhar@berkeley.edu lzipursky@mednet.ucla.edu
S. Lawrence Zipursky
1Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
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  • For correspondence: kshekhar@berkeley.edu lzipursky@mednet.ucla.edu
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ABSTRACT

The role of postnatal experience in sculpting cortical circuitry, while long appreciated, is poorly understood at the level of cell types. We explore this in the mouse primary visual cortex (V1) using single-nucleus RNA-sequencing, visual deprivation, genetics, and functional imaging. We find that vision selectively drives the specification of glutamatergic cell types in upper layers (L) (L2/3/4), while deeper-layer glutamatergic, GABAergic, and non-neuronal cell types are established prior to eye opening. L2/3 cell types form an experience-dependent spatial continuum defined by the graded expression of ∼200 genes, including regulators of cell adhesion and synapse formation. Vision-dependent regulation of one of these genes, encoding the inhibitory synaptic cell adhesion molecule IGSF9b, is required for the normal development of binocular responses in L2/3. In summary, vision preferentially regulates the development of upper-layer glutamatergic cell types through the regulation of cell type-specific gene expression programs.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/shekharlab/mouseVC

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 21, 2021.
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Vision-dependent specification of cell types and function in the developing cortex
Sarah Cheng, Salwan Butrus, Liming Tan, Vincent Xu, Srikant Sagireddy, Joshua T. Trachtenberg, Karthik Shekhar, S. Lawrence Zipursky
bioRxiv 2021.08.10.455824; doi: https://doi.org/10.1101/2021.08.10.455824
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Vision-dependent specification of cell types and function in the developing cortex
Sarah Cheng, Salwan Butrus, Liming Tan, Vincent Xu, Srikant Sagireddy, Joshua T. Trachtenberg, Karthik Shekhar, S. Lawrence Zipursky
bioRxiv 2021.08.10.455824; doi: https://doi.org/10.1101/2021.08.10.455824

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