title: Proliferative defects and formation of a double cortex in mice lacking Mltt4 and Cdh2 in the dorsal telencephalon.
abstract: Radial glial cells (RGCs) in the ventricular neuroepithelium of the dorsal telencephalon are the progenitor cells for neocortical projection neurons and astrocytes. Here we show that the adherens junction proteins afadin and CDH2 are critical for the control of cell proliferation in the dorsal telencephalon and for the formation of its normal laminar structure. Inactivation of afadin or CDH2 in the dorsal telencephalon leads to a phenotype resembling subcortical band heterotopia, also known as "double cortex," a brain malformation in which heterotopic gray matter is interposed between zones of white matter. Adherens junctions between RGCs are disrupted in the mutants, progenitor cells are widely dispersed throughout the developing neocortex, and their proliferation is dramatically increased. Major subtypes of neocortical projection neurons are generated, but their integration into cell layers is disrupted. Our findings suggest that defects in adherens junctions components in mice massively affects progenitor cell proliferation and leads to a double cortex-like phenotype.
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, and.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil-Sanz
authors.affiliation: Brain Institute, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte 59056-450, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Landeira
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, and.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ramos
authors.affiliation: Brain Institute, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte 59056-450, Brazil.
authors.forename: Marcos R
authors.initials: MR
authors.lastname: Costa
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, and umueller@scripps.edu.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Müller
mesh_terms: D000367:Age Factors; D000818:Animals; D015820:Cadherins / Q000172:deficiency* / Q000235:genetics; D049109:Cell Proliferation; D000089622:Doublecortin Domain Proteins; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D054220:Malformations of Cortical Development / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000172:deficiency* / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D013687:Telencephalon / Q000002:abnormalities / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D015820:Cadherins; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010751:Phosphopyruvate Hydratase; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000099260:Empty Spiracles Homeobox Proteins; C511143:Bcl11b protein, mouse; C489083:Cdh2 protein, mouse; C108835:afadin
keywords: CDH2; afadin; double cortex; neocortex; progenitor; radial glia
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