Abstract:
Here, we report the first characterization of the effects resulting from the manipulation of Soluble-Lamin Associated Protein (SLAP) expression during mammalian brain development. We found that SLAP localizes to the nuclear envelope and when overexpressed causes changes in nuclear morphology and lengthening of mitosis. SLAP overexpression in apical progenitors of the developing mouse brain altered asymmetric cell division, neurogenic commitment and neuronal migration ultimately resulting in unbalance in the proportion of upper, relative to deeper, neuronal layers. Several of these effects were also recapitulated upon Cas9-mediated knockdown. Ultimately, SLAP overexpression during development resulted in a reduction in subcortical projections of young mice and, notably, reduced their exploratory behavior. Our study shows the potential relevance of the previously uncharacterized nuclear envelope protein SLAP in neurodevelopmental disorders.
摘要:
这里,我们报道了在哺乳动物大脑发育过程中通过操纵可溶性Lamin相关蛋白(SLAP)表达而产生的影响的第一个特征。我们发现SLAP定位于核包膜,当过度表达时会引起核形态变化和有丝分裂延长。SLAP在发育中的小鼠大脑的顶端祖细胞中的过度表达改变了不对称细胞分裂,神经性承诺和神经元迁移最终导致上,相对于更深,神经元层。在Cas9介导的敲低时也概述了这些作用中的一些。最终,SLAP在发育过程中的过度表达导致幼鼠的皮质下投射减少,特别是,减少了他们的探索行为。我们的研究显示了先前未表征的核包膜蛋白SLAP在神经发育障碍中的潜在相关性。