Transcriptional profiling of embryos lacking Flvcr1

Flvcr1 is a heme transporter involved in multiple processes. Here we invetigated the role of this transporter in brain development in mice. Deletion of Flvcr1 in nerual progenitors leads to metabolic collapse of neural progenitors and cortical disruption. Using transcriptional profiling, we show that brains of these embryos expressed reduced levels of electron transport chain components and increased levels of heme metabolic genes. These results implicate Flvcr1 in brain development through control of the metabolic state in neural progenitors. We inactivated Flvcr1 in neural progenitors using Nestin-Cre and isolated brains from 3 control and 3 mutant embryos at E14.5.

Flvcr1是一种参与多种生物学过程的血红素转运蛋白。本研究以小鼠为模型，探究了该转运蛋白在大脑发育过程中的作用。在神经前体细胞中敲除Flvcr1，会导致神经前体细胞代谢崩溃以及皮层结构紊乱。通过转录组分析（transcriptional profiling），我们发现该类胚胎的脑组织中，电子传递链复合物的表达水平显著下调，而血红素代谢相关基因的表达水平则显著上调。上述结果表明，Flvcr1可通过调控神经前体细胞的代谢状态参与小鼠大脑发育过程。本研究利用Nestin-Cre重组酶系统在神经前体细胞中特异性失活Flvcr1，并于胚胎发育第14.5天（E14.5）分离得到3只对照组胚胎与3只突变体胚胎的脑组织。