Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity

Maria J. Galazo; Jason G. Emsley; Jeffrey D. Macklis

doi:10.1016/j.neuron.2016.05.024

Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity

Maria J. Galazo, Jason G. Emsley, Jeffrey D. Macklis

Research output: Contribution to journal › Article › peer-review

47 Citations (Scopus)

Abstract

Corticothalamic projection neurons (CThPN) are a diverse set of neurons, critical for function of the neocortex. CThPN development and diversity need to be precisely regulated, but little is known about molecular controls over their differentiation and functional specialization, critically limiting understanding of cortical development and complexity. We report the identification of a set of genes that both define CThPN and likely control their differentiation, diversity, and function. We selected the CThPN-specific transcriptional coregulator Fog2 for functional analysis. We identify that Fog2 controls CThPN molecular differentiation, axonal targeting, and diversity, in part by regulating the expression level of Ctip2 by CThPN, via combinatorial interactions with other molecular controls. Loss of Fog2 specifically disrupts differentiation of subsets of CThPN specialized in motor function, indicating that Fog2 coordinates subtype and functional-area differentiation. These results confirm that we identified key controls over CThPN development and identify Fog2 as a critical control over CThPN diversity.

Original language	English
Pages (from-to)	90-106
Number of pages	17
Journal	Neuron
Volume	91
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2016.05.024
Publication status	Published - Jul 6 2016
Externally published	Yes

Bibliographical note

Funding Information:
We thank B.J. Molyneaux for invaluable help in setting up retrograde labeling, FACS, and microarray experiments and for insightful comments on earlier versions of this manuscript; P. Arlotta and D. Jabaudon for important early assistance with microarray analysis; S. Tevosian and N. Manuylov for generously sharing Fog2 floxed mice before publication; K. Quinn, A. Palmer, T. Yamamoto, K. Billmers, and E.L. Gornstein for technical assistance; D. Dombkowski for assistance with FACS; L. Goodrich for generously sharing CTV-Fog2 mice; C. Lois for plasmids; H. Padmanabhan, V. Sahni, and J.L. MacDonald for enlightening scientific discussions; and other members of the Macklis lab for helpful suggestions. This work was supported by grants from the NIH (R01NS45523, with additional infrastructure support by R37NS41590, R01NS49553, R01NS75672) and the Harvard Stem Cell Institute. M.J.G. was partially supported by fellowships from CajaMadrid Foundation and the Spanish Ministry of Education. J.G.E. was partially supported by fellowships from the Heart and Stroke Foundation of Canada and the Paralyzed Veterans of America/Travis Roy Foundation. J.D.M. is an Allen Distinguished Investigator of the Paul G. Allen Frontiers Group.

Publisher Copyright:
© 2016 Elsevier Inc.

ASJC Scopus Subject Areas

General Neuroscience

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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10.1016/j.neuron.2016.05.024

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title = "Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity",

abstract = "Corticothalamic projection neurons (CThPN) are a diverse set of neurons, critical for function of the neocortex. CThPN development and diversity need to be precisely regulated, but little is known about molecular controls over their differentiation and functional specialization, critically limiting understanding of cortical development and complexity. We report the identification of a set of genes that both define CThPN and likely control their differentiation, diversity, and function. We selected the CThPN-specific transcriptional coregulator Fog2 for functional analysis. We identify that Fog2 controls CThPN molecular differentiation, axonal targeting, and diversity, in part by regulating the expression level of Ctip2 by CThPN, via combinatorial interactions with other molecular controls. Loss of Fog2 specifically disrupts differentiation of subsets of CThPN specialized in motor function, indicating that Fog2 coordinates subtype and functional-area differentiation. These results confirm that we identified key controls over CThPN development and identify Fog2 as a critical control over CThPN diversity.",

author = "Galazo, {Maria J.} and Emsley, {Jason G.} and Macklis, {Jeffrey D.}",

note = "Funding Information: We thank B.J. Molyneaux for invaluable help in setting up retrograde labeling, FACS, and microarray experiments and for insightful comments on earlier versions of this manuscript; P. Arlotta and D. Jabaudon for important early assistance with microarray analysis; S. Tevosian and N. Manuylov for generously sharing Fog2 floxed mice before publication; K. Quinn, A. Palmer, T. Yamamoto, K. Billmers, and E.L. Gornstein for technical assistance; D. Dombkowski for assistance with FACS; L. Goodrich for generously sharing CTV-Fog2 mice; C. Lois for plasmids; H. Padmanabhan, V. Sahni, and J.L. MacDonald for enlightening scientific discussions; and other members of the Macklis lab for helpful suggestions. This work was supported by grants from the NIH (R01NS45523, with additional infrastructure support by R37NS41590, R01NS49553, R01NS75672) and the Harvard Stem Cell Institute. M.J.G. was partially supported by fellowships from CajaMadrid Foundation and the Spanish Ministry of Education. J.G.E. was partially supported by fellowships from the Heart and Stroke Foundation of Canada and the Paralyzed Veterans of America/Travis Roy Foundation. J.D.M. is an Allen Distinguished Investigator of the Paul G. Allen Frontiers Group. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

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doi = "10.1016/j.neuron.2016.05.024",

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AU - Macklis, Jeffrey D.

N1 - Funding Information: We thank B.J. Molyneaux for invaluable help in setting up retrograde labeling, FACS, and microarray experiments and for insightful comments on earlier versions of this manuscript; P. Arlotta and D. Jabaudon for important early assistance with microarray analysis; S. Tevosian and N. Manuylov for generously sharing Fog2 floxed mice before publication; K. Quinn, A. Palmer, T. Yamamoto, K. Billmers, and E.L. Gornstein for technical assistance; D. Dombkowski for assistance with FACS; L. Goodrich for generously sharing CTV-Fog2 mice; C. Lois for plasmids; H. Padmanabhan, V. Sahni, and J.L. MacDonald for enlightening scientific discussions; and other members of the Macklis lab for helpful suggestions. This work was supported by grants from the NIH (R01NS45523, with additional infrastructure support by R37NS41590, R01NS49553, R01NS75672) and the Harvard Stem Cell Institute. M.J.G. was partially supported by fellowships from CajaMadrid Foundation and the Spanish Ministry of Education. J.G.E. was partially supported by fellowships from the Heart and Stroke Foundation of Canada and the Paralyzed Veterans of America/Travis Roy Foundation. J.D.M. is an Allen Distinguished Investigator of the Paul G. Allen Frontiers Group. Publisher Copyright: © 2016 Elsevier Inc.

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N2 - Corticothalamic projection neurons (CThPN) are a diverse set of neurons, critical for function of the neocortex. CThPN development and diversity need to be precisely regulated, but little is known about molecular controls over their differentiation and functional specialization, critically limiting understanding of cortical development and complexity. We report the identification of a set of genes that both define CThPN and likely control their differentiation, diversity, and function. We selected the CThPN-specific transcriptional coregulator Fog2 for functional analysis. We identify that Fog2 controls CThPN molecular differentiation, axonal targeting, and diversity, in part by regulating the expression level of Ctip2 by CThPN, via combinatorial interactions with other molecular controls. Loss of Fog2 specifically disrupts differentiation of subsets of CThPN specialized in motor function, indicating that Fog2 coordinates subtype and functional-area differentiation. These results confirm that we identified key controls over CThPN development and identify Fog2 as a critical control over CThPN diversity.

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Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

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