Abstract
BackgroundIn developing tissues, cell polarity and tissue architecture play essential roles in the regulation of proliferation and differentiation. During cerebral cortical development, adherens junctions link highly polarized radial glial cells in a neurogenic niche that controls their behavior. How adherens junctions regulate radial glial cell polarity and/or differentiation in mammalian cortical development is poorly understood.ResultsConditional deletion of Afadin, a protein required for formation and maintenance of epithelial tissues, leads to abnormalities in radial glial cell polarity and subsequent loss of adherens junctions. We observed increased numbers of obliquely-oriented progenitor cell divisions, increased exit from the ventricular zone neuroepithelium, and increased production of intermediate progenitors.ConclusionsTogether, these findings indicate that Afadin plays an essential role in regulating apical-basal polarity and adherens junction integrity of radial glial cells, and suggest that epithelial architecture plays an important role in radial glial identity by regulating mitotic orientation and preventing premature exit from the neurogenic niche.
Highlights
In developing tissues, cell polarity and tissue architecture play essential roles in the regulation of proliferation and differentiation
Cortical neurons develop from a layer of proliferating progenitor cells, called the ventricular zone (VZ), which lines the lateral ventricles of the embryonic brain
Afadin is essential for the maintenance of adherens junctions in the neuroepithelium Previous studies using Emx1-Cre (Emx1-Cre; Mllt4fl/fl mice) showed that conditional deletion of Afadin from developing cortical radial glial cells at E9.5 resulted in hyperproliferation and radial glial disorganization [12, 18]
Summary
Cell polarity and tissue architecture play essential roles in the regulation of proliferation and differentiation. How adherens junctions regulate radial glial cell polarity and/or differentiation in mammalian cortical development is poorly understood. Recent studies have described unequal inheritance of determinants known to play important roles in establishing and maintaining asymmetric cell fate in mammalian cortical development [1]. Neuroepithelial and radial glial cells are highly polarized cells, having distinct apical and basolateral domains with characteristic morphology and associated protein complexes [3, 4]. This intrinsic apicalbasal polarity provides an attractive mechanism to allocate subcellular determinants unequally during mitosis. By orienting the angle of mitotic cleavage, cleavage furrows could segregate determinants symmetrically or asymmetrically to produce equal or unequal daughter cells [5]
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