title: Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS.
abstract: Neuroepithelial attachments at adherens junctions are essential for the self-renewal of neural stem and progenitor cells and the polarized organization of the developing central nervous system. The balance between stem cell maintenance and differentiation depends on the precise assembly and disassembly of these adhesive contacts, but the gene regulatory mechanisms orchestrating this process are not known. Here, we demonstrate that two Forkhead transcription factors, Foxp2 and Foxp4, are progressively expressed upon neural differentiation in the spinal cord. Elevated expression of either Foxp represses the expression of a key component of adherens junctions, N-cadherin, and promotes the detachment of differentiating neurons from the neuroepithelium. Conversely, inactivation of Foxp2 and Foxp4 function in both chick and mouse results in a spectrum of neural tube defects associated with neuroepithelial disorganization and enhanced progenitor maintenance. Together, these data reveal a Foxp-based transcriptional mechanism that regulates the integrity and cytoarchitecture of neuroepithelial progenitors.
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine at UCLA, 610 Charles Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Rousso
authors.forename: Caroline Alayne
authors.initials: CA
authors.lastname: Pearson
authors.forename: Zachary B
authors.initials: ZB
authors.lastname: Gaber
authors.forename: Amaya
authors.initials: A
authors.lastname: Miquelajauregui
authors.forename: Shanru
authors.initials: S
authors.lastname: Li
authors.forename: Carlos
authors.initials: C
authors.lastname: Portera-Cailliau
authors.forename: Edward E
authors.initials: EE
authors.lastname: Morrisey
authors.forename: Bennett G
authors.initials: BG
authors.lastname: Novitch
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D019521:Body Patterning / Q000235:genetics*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002490:Central Nervous System / Q000166:cytology* / Q000201:enzymology; D002642:Chick Embryo; D018274:Electroporation; D004622:Embryo, Mammalian; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D046569:Neuroepithelial Cells / Q000502:physiology*; D000076104:Oligodendrocyte Transcription Factor 2; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D051858:Forkhead Transcription Factors; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D010751:Phosphopyruvate Hydratase; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; C489083:Cdh2 protein, mouse; C472854:Foxp4 protein, mouse; C512773:Olig2 protein, mouse; C527783:Sox2 protein, mouse