FOXP1 Promotes Embryonic Neural Stem Cell Differentiation by Repressing Jagged1 Expression
Summary: Mutations in FOXP1 have been linked to neurodevelopmental disorders including intellectual disability and autism; however, the underlying molecular mechanisms remain ill-defined. Here, we demonstrate with RNA and chromatin immunoprecipitation sequencing that FOXP1 directly regulates genes c...
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doaj-795d72b0cce14820b0582e1b90743cb82020-11-24T21:43:37ZengElsevierStem Cell Reports2213-67112017-11-019515301545FOXP1 Promotes Embryonic Neural Stem Cell Differentiation by Repressing Jagged1 ExpressionLuca Braccioli0Stephin J. Vervoort1Youri Adolfs2Cobi J. Heijnen3Onur Basak4R. Jeroen Pasterkamp5Cora H. Nijboer6Paul J. Coffer7Laboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, Utrecht 3508 AB, the Netherlands; Center for Molecular Medicine and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht 3584 CT, the NetherlandsCenter for Molecular Medicine and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht 3584 CT, the NetherlandsDepartment of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, the NetherlandsLaboratory of Neuroimmunology, Department of Symptom Research, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAHubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT Utrecht, the NetherlandsDepartment of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, the NetherlandsLaboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, Utrecht 3508 AB, the Netherlands; Corresponding authorCenter for Molecular Medicine and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht 3584 CT, the Netherlands; Corresponding authorSummary: Mutations in FOXP1 have been linked to neurodevelopmental disorders including intellectual disability and autism; however, the underlying molecular mechanisms remain ill-defined. Here, we demonstrate with RNA and chromatin immunoprecipitation sequencing that FOXP1 directly regulates genes controlling neurogenesis. We show that FOXP1 is expressed in embryonic neural stem cells (NSCs), and modulation of FOXP1 expression affects both neuron and astrocyte differentiation. Using a murine model of cortical development, FOXP1-knockdown in utero was found to reduce NSC differentiation and migration during corticogenesis. Furthermore, transplantation of FOXP1-knockdown NSCs in neonatal mice after hypoxia-ischemia challenge demonstrated that FOXP1 is also required for neuronal differentiation and functionality in vivo. FOXP1 was found to repress the expression of Notch pathway genes including the Notch-ligand Jagged1, resulting in inhibition of Notch signaling. Finally, blockade of Jagged1 in FOXP1-knockdown NSCs rescued neuronal differentiation in vitro. Together, these data support a role for FOXP1 in regulating embryonic NSC differentiation by modulating Notch signaling. : In this issue of Stem Cell Reports, Braccioli et al. describe how FOXP1 promotes embryonic neural stem cell differentiation both in vitro and in vivo by transcriptionally regulating pro-neural genes and by repressing the Notch-ligand Jagged1. Keywords: embryonic neural stem cells, NSC, differentiation, transcription, FOXP1, Notchhttp://www.sciencedirect.com/science/article/pii/S2213671117304678 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Luca Braccioli Stephin J. Vervoort Youri Adolfs Cobi J. Heijnen Onur Basak R. Jeroen Pasterkamp Cora H. Nijboer Paul J. Coffer |
spellingShingle |
Luca Braccioli Stephin J. Vervoort Youri Adolfs Cobi J. Heijnen Onur Basak R. Jeroen Pasterkamp Cora H. Nijboer Paul J. Coffer FOXP1 Promotes Embryonic Neural Stem Cell Differentiation by Repressing Jagged1 Expression Stem Cell Reports |
author_facet |
Luca Braccioli Stephin J. Vervoort Youri Adolfs Cobi J. Heijnen Onur Basak R. Jeroen Pasterkamp Cora H. Nijboer Paul J. Coffer |
author_sort |
Luca Braccioli |
title |
FOXP1 Promotes Embryonic Neural Stem Cell Differentiation by Repressing Jagged1 Expression |
title_short |
FOXP1 Promotes Embryonic Neural Stem Cell Differentiation by Repressing Jagged1 Expression |
title_full |
FOXP1 Promotes Embryonic Neural Stem Cell Differentiation by Repressing Jagged1 Expression |
title_fullStr |
FOXP1 Promotes Embryonic Neural Stem Cell Differentiation by Repressing Jagged1 Expression |
title_full_unstemmed |
FOXP1 Promotes Embryonic Neural Stem Cell Differentiation by Repressing Jagged1 Expression |
title_sort |
foxp1 promotes embryonic neural stem cell differentiation by repressing jagged1 expression |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2017-11-01 |
description |
Summary: Mutations in FOXP1 have been linked to neurodevelopmental disorders including intellectual disability and autism; however, the underlying molecular mechanisms remain ill-defined. Here, we demonstrate with RNA and chromatin immunoprecipitation sequencing that FOXP1 directly regulates genes controlling neurogenesis. We show that FOXP1 is expressed in embryonic neural stem cells (NSCs), and modulation of FOXP1 expression affects both neuron and astrocyte differentiation. Using a murine model of cortical development, FOXP1-knockdown in utero was found to reduce NSC differentiation and migration during corticogenesis. Furthermore, transplantation of FOXP1-knockdown NSCs in neonatal mice after hypoxia-ischemia challenge demonstrated that FOXP1 is also required for neuronal differentiation and functionality in vivo. FOXP1 was found to repress the expression of Notch pathway genes including the Notch-ligand Jagged1, resulting in inhibition of Notch signaling. Finally, blockade of Jagged1 in FOXP1-knockdown NSCs rescued neuronal differentiation in vitro. Together, these data support a role for FOXP1 in regulating embryonic NSC differentiation by modulating Notch signaling. : In this issue of Stem Cell Reports, Braccioli et al. describe how FOXP1 promotes embryonic neural stem cell differentiation both in vitro and in vivo by transcriptionally regulating pro-neural genes and by repressing the Notch-ligand Jagged1. Keywords: embryonic neural stem cells, NSC, differentiation, transcription, FOXP1, Notch |
url |
http://www.sciencedirect.com/science/article/pii/S2213671117304678 |
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