Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, and.
Brain Institute, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte 59056-450, Brazil.
J Neurosci. 2014 Aug 6;34(32):10475-87. doi: 10.1523/JNEUROSCI.1793-14.2014.
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.
室管膜下神经上皮中的放射状胶质细胞（RGCs）是新皮层投射神经元和星形胶质细胞的祖细胞。在这里，我们表明黏着连接蛋白 afadin 和 CDH2 对于控制背侧端脑的细胞增殖以及形成其正常的层状结构至关重要。在背侧端脑中失活 afadin 或 CDH2 会导致类似于皮质下带异位的表型，也称为“双皮质”，这是一种脑畸形，其中异位灰质插入在白质区域之间。在突变体中，RGC 之间的黏着连接被破坏，祖细胞广泛分散在整个发育中的新皮层中，其增殖显著增加。新皮层投射神经元的主要亚型被生成，但它们整合到细胞层中被破坏。我们的研究结果表明，黏着连接蛋白成分的缺陷在小鼠中极大地影响了祖细胞的增殖，并导致类似于双皮质的表型。
