Department of Neurological Surgery, University of California, San Francisco, USA.
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, USA.
Cereb Cortex. 2018 Jun 1;28(6):1946-1958. doi: 10.1093/cercor/bhx101.
The neocortex of primates, including humans, contains more abundant and diverse inhibitory neurons compared with rodents, but the molecular foundations of these observations are unknown. Through integrative gene coexpression analysis, we determined a consensus transcriptional profile of GABAergic neurons in mid-gestation human neocortex. By comparing this profile to genes expressed in GABAergic neurons purified from neonatal mouse neocortex, we identified conserved and distinct aspects of gene expression in these cells between the species. We show here that the calcium-binding protein secretagogin (SCGN) is robustly expressed by neocortical GABAergic neurons derived from caudal ganglionic eminences (CGE) and lateral ganglionic eminences during human but not mouse brain development. Through electrophysiological and morphometric analyses, we examined the effects of SCGN expression on GABAergic neuron function and form. Forced expression of SCGN in CGE-derived mouse GABAergic neurons significantly increased total neurite length and arbor complexity following transplantation into mouse neocortex, revealing a molecular pathway that contributes to morphological differences in these cells between rodents and primates.
灵长类动物（包括人类）的新皮层含有比啮齿动物更丰富和多样的抑制性神经元，但这些观察结果的分子基础尚不清楚。通过整合基因共表达分析，我们确定了中孕期人类新皮层 GABA 能神经元的共识转录特征。通过将该特征与从新生小鼠新皮层中纯化的 GABA 能神经元表达的基因进行比较，我们确定了这些细胞在物种间表达的基因的保守和独特方面。我们在这里表明，钙结合蛋白分泌素（SCGN）在人类而非小鼠大脑发育过程中，由尾状神经节隆起（CGE）和外侧神经节隆起衍生的新皮层 GABA 能神经元中强烈表达。通过电生理和形态计量分析，我们研究了 SCGN 表达对 GABA 能神经元功能和形态的影响。在将 SCGN 强制表达于源自 CGE 的小鼠 GABA 能神经元后，在移植到小鼠新皮层后，总神经突长度和分支复杂度显著增加，揭示了一种分子途径，该途径有助于这些细胞在啮齿动物和灵长类动物之间的形态差异。
