Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis.
Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis.
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DOI：
10.1038/ncomms9265
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发表时间：
2015-09-15
影响因子：
16.6
通讯作者：
Ferguson-Smith AC
中科院分区：
文献类型：
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作者：
Ferrón SR;Radford EJ;Domingo-Muelas A;Kleine I;Ramme A;Gray D;Sandovici I;Constancia M;Ward A;Menheniott TR;Ferguson-Smith AC
基因组印记与神经原性小生境中基因剂量的控制有关。在这里，我们解决的重要性Igf2印迹小鼠成年神经发生在脑室下区（SVZ）和在海马体的颗粒下区（SGZ）在体内。在SVZ中，旁分泌IGF2是一种脑脊液和内皮源性神经原性因子，需要双等位基因表达，突变体具有减少的干细胞库激活和受损的嗅球神经发生。与此相反，Igf2是印记在海马作为自分泌因子表达的神经干细胞（NSC）仅从父亲的等位基因。血管中Igf2的条件性突变证实了内皮源性IGF2有助于SVZ中的NSC维持，而不是SGZ中的NSC维持，并且这是由血管隔室中IGF2的双等位基因表达调节的。我们的研究结果表明，一个监管决定印记或不是一个功能上重要的机制，转录剂量控制在成人神经发生。 已知通过基因组印记的某些基因的选择性双等位基因表达在控制成年哺乳动物脑中的神经发生中起作用。在这里，作者研究了印记在IGF2剂量控制中的作用及其与IGF2在小鼠大脑中作为神经源性调节剂的功能的相关性。
Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis. Selective biallelic expression of certain genes through genomic imprinting are known to play a role in controlling neurogenesis in the adult mammalian brain. Here the authors investigate the role of imprinting in the dosage control of Igf2 and its relevance for the function of IGF2 as a neurogenic regulator in the mouse brain.