Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits

Hanna E Stevens; Karen M Smith; M Elisabetta Maragnoli; Devon Fagel; Erzsi Borok; Marya Shanabrough; Tamas L Horvath; Flora M Vaccarino

doi:10.1523/jneurosci.5837-09.2010

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Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits

Journal article

Open access

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Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits

Hanna E Stevens, Karen M Smith, M Elisabetta Maragnoli, Devon Fagel, Erzsi Borok, Marya Shanabrough, Tamas L Horvath and Flora M Vaccarino

The Journal of neuroscience, Vol.30(16), pp.5590-5602

04/21/2010

DOI: 10.1523/jneurosci.5837-09.2010

PMCID: PMC2868832

PMID: 20410112

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Abstract

To understand the role of specific fibroblast growth factor receptors (FGFRs) in cortical development, we conditionally inactivated Fgfr2 or both Fgfr1 and Fgfr2 [Fgfr2 conditional knock-out (cKO) or double knock-out mice, respectively] in radial glial cells of the dorsal telencephalon. Fgfr1 and Fgfr2 are necessary for the attainment of a normal number of excitatory neurons in the cerebral cortex. The action of FGF receptors appears to be through increasing self-renewal of neuronal precursors within the ventricular zone. Volume measurements, assessments of excitatory neuron number, and areal marker expression suggested that the proper formation of the medial prefrontal cortex (mPFC) depends on the function of Fgfr2, whereas Fgfr1 together with Fgfr2 control excitatory cortical neuron development within the entire cerebral cortex. Fgfr2 cKO mice had fewer and smaller glutamate synaptic terminals in the bed nuclei of the stria terminalis (BST), a projection area for mPFC cortical neurons. Furthermore, Fgfr2 cKO mice showed secondary decreases in GABAergic neurons in the BST and septum. These data demonstrate that FGFR2 signaling expands the number of excitatory neurons in the mPFC and secondarily influences target neurons in subcortical stations of the limbic system.

Nerve Net - embryology

Nerve Net - growth & development

Prefrontal Cortex - embryology

Limbic System - growth & development

Cell Proliferation

Humans

Neural Pathways - growth & development

Mice, Transgenic

Limbic System - metabolism

Prefrontal Cortex - growth & development

Limbic System - embryology

Mice, Knockout

Pregnancy

Receptor, Fibroblast Growth Factor, Type 2 - physiology

Animals

Nerve Net - metabolism

Prefrontal Cortex - metabolism

Neural Pathways - metabolism

Female

Mice

Neural Pathways - embryology

Receptor, Fibroblast Growth Factor, Type 2 - deficiency

Receptor, Fibroblast Growth Factor, Type 2 - genetics

Details

Title: Subtitle: Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits
Creators: Hanna E Stevens - Child Study Center, Yale University, New Haven, Connecticut 06520, USA
Karen M Smith
M Elisabetta Maragnoli
Devon Fagel
Erzsi Borok
Marya Shanabrough
Tamas L Horvath
Flora M Vaccarino
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.30(16), pp.5590-5602
DOI: 10.1523/jneurosci.5837-09.2010
PMID: 20410112
PMCID: PMC2868832
NLM abbreviation: J Neurosci
ISSN: 1529-2401
eISSN: 1529-2401
Publisher: United States
Grant note: R01 MH067715-07 / NIMH NIH HHS R25 MH077823 / NIMH NIH HHS T32 MH018268 / NIMH NIH HHS R01 MH067715-06A1 / NIMH NIH HHS R01 MH067715 / NIMH NIH HHS R25 MH071584 / NIMH NIH HHS
Language: English
Date published: 04/21/2010
Academic Unit: Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984003932102771

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