Proliferative defects and formation of a double cortex in mice lacking Mltt4 and Cdh2 in the dorsal telencephalon

Cristina Gil-Sanz; Bruna Landeira; Cynthia Ramos; Marcos R Costa; Ulrich Müller

doi:10.1523/JNEUROSCI.1793-14.2014

Proliferative defects and formation of a double cortex in mice lacking Mltt4 and Cdh2 in the dorsal telencephalon

J Neurosci. 2014 Aug 6;34(32):10475-87. doi: 10.1523/JNEUROSCI.1793-14.2014.

Authors

Cristina Gil-Sanz¹, Bruna Landeira², Cynthia Ramos¹, Marcos R Costa², Ulrich Müller³

Affiliations

¹ Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, and.
² Brain Institute, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte 59056-450, Brazil.
³ Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, and umueller@scripps.edu.

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.

Keywords: CDH2; afadin; double cortex; neocortex; progenitor; radial glia.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
Cadherins / deficiency*
Cadherins / genetics
Cell Proliferation*
Doublecortin Domain Proteins
Embryo, Mammalian
Gene Expression Regulation, Developmental / genetics
Glial Fibrillary Acidic Protein / metabolism
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Malformations of Cortical Development / genetics*
Malformations of Cortical Development / pathology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microfilament Proteins / deficiency*
Microfilament Proteins / genetics
Microtubule-Associated Proteins / metabolism
Neuropeptides / metabolism
Phosphopyruvate Hydratase / metabolism
Repressor Proteins / metabolism
Stem Cells / physiology
Telencephalon / abnormalities
Telencephalon / pathology*
Transcription Factors / genetics
Tumor Suppressor Proteins / metabolism

Substances

Bcl11b protein, mouse
Cadherins
Cdh2 protein, mouse
Doublecortin Domain Proteins
Glial Fibrillary Acidic Protein
Homeodomain Proteins
Microfilament Proteins
Microtubule-Associated Proteins
Neuropeptides
Repressor Proteins
Transcription Factors
Tumor Suppressor Proteins
afadin
empty spiracles homeobox proteins
Phosphopyruvate Hydratase

Abstract

Publication types

MeSH terms

Substances

Grants and funding