FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways
FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits....
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2014-09-01
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doaj-bdc926407ff44187bcd9201aaaa4a0592020-11-24T21:44:56ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-09-01810.3389/fncel.2014.00305107696FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathwaysPaolo eDevanna0Jeroen eMiddelbeek1Sonja Catherine Vernes2Sonja Catherine Vernes3Max Planck Institute for PsycholinguisticsRadboud UniversityMax Planck Institute for PsycholinguisticsRadboud UniversityFOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells.http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00305/fullForkhead Transcription FactorsLanguageneuronal migrationneuron differentiationRetinoic acidFoxP2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paolo eDevanna Jeroen eMiddelbeek Sonja Catherine Vernes Sonja Catherine Vernes |
spellingShingle |
Paolo eDevanna Jeroen eMiddelbeek Sonja Catherine Vernes Sonja Catherine Vernes FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways Frontiers in Cellular Neuroscience Forkhead Transcription Factors Language neuronal migration neuron differentiation Retinoic acid FoxP2 |
author_facet |
Paolo eDevanna Jeroen eMiddelbeek Sonja Catherine Vernes Sonja Catherine Vernes |
author_sort |
Paolo eDevanna |
title |
FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways |
title_short |
FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways |
title_full |
FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways |
title_fullStr |
FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways |
title_full_unstemmed |
FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways |
title_sort |
foxp2 drives neuronal differentiation by interacting with retinoic acid signaling pathways |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2014-09-01 |
description |
FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells. |
topic |
Forkhead Transcription Factors Language neuronal migration neuron differentiation Retinoic acid FoxP2 |
url |
http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00305/full |
work_keys_str_mv |
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