The hypothalamic-neurohypophyseal system: from genome to physiology.
The hypothalamic-neurohypophyseal system: from genome to physiology.
复制标题
下丘脑-神经垂体系统：从基因组到生理学。
DOI：
10.1111/j.1365-2826.2011.02241.x
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发表时间：
2012
影响因子：
3.2
通讯作者：
Japundzic-Zigon,N
中科院分区：
文献类型：
--
作者：
Murphy,D;Konopacka,A;Hindmarch,C;Paton,JFR;Sweedler,JV;Gillette,MU;Ueta,Y;Grinevich,V;Lozic,M;Japundzic-Zigon,N
大量哺乳动物物种基因组的阐明产生了大量的数据，作为生理学研究的基础。这些努力也产生了令人惊讶的结果，其中最重要的是揭示了制造哺乳动物所需的蛋白质编码基因的数量仅为22333（给或取）。 然而，这个小数目掩盖了一个意想不到的复杂性，这是最近才被揭示的基因组研究的结果。这种复杂性在以下几个层面上是显而易见的：（i）顺式调控序列;（ii）非编码和反义mRNA，其中大多数没有已知的功能;（iii）选择性剪接，导致从单个基因编码的前体转录物产生多个细微不同的成熟mRNA;（iv）翻译后加工和修饰。在这篇综述中，我们研究了在下丘脑-神经垂体系统（HNS）的基因表达，调控和功能的背景下，正在采取的步骤来破译基因组的复杂性。五个独特的故事解释：（i）使用转录组学来鉴定参与生理反应的基因，（脱水）和病理性（ii）使用质谱法在单细胞水平鉴定HNS中的生物活性肽，并测量玻璃体释放;（iii）使用表达融合转基因的转基因系，（通过杂交）产生双转基因系，可用于研究HNS中的加压素（AVP）和催产素（OXT）神经元，以及它们的神经解剖学、电生理学和暴露于任何给定刺激后的激活;（iv）使用病毒载体证明体-树突释放的AVP通过与局部胞体和树突上的V1 a受体结合在心血管稳态中发挥重要作用;（v）使用病毒介导的光遗传学来剖析OXT和AVP在调节各种行为中的作用。
The elucidation of the genomes of a large number of mammalian species has produced a huge amount of data on which to base physiological studies. These endeavours have also produced surprises, not least of which has been the revelation that the number of protein coding genes needed to make a mammal is only 22 333 (give or take). However, this small number belies an unanticipated complexity that has only recently been revealed as a result of genomic studies. This complexity is evident at a number of levels: (i)cis‐regulatory sequences; (ii) noncoding and antisense mRNAs, most of which have no known function; (iii) alternative splicing that results in the generation of multiple, subtly different mature mRNAs from the precursor transcript encoded by a single gene; and (iv) post‐translational processing and modification. In this review, we examine the steps being taken to decipher genome complexity in the context of gene expression, regulation and function in the hypothalamic‐neurohypophyseal system (HNS). Five unique stories explain: (i) the use of transcriptomics to identify genes involved in the response to physiological (dehydration) and pathological (hypertension) cues; (ii) the use of mass spectrometry for single‐cell level identification of biological active peptides in the HNS, and to measurein vitrorelease; (iii) the use of transgenic lines that express fusion transgenes enabling (by cross‐breeding) the generation of double transgenic lines that can be used to study vasopressin (AVP) and oxytocin (OXT) neurones in the HNS, as well as their neuroanatomy, electrophysiology and activation upon exposure to any given stimulus; (iv) the use of viral vectors to demonstrate that somato‐dendritically released AVP plays an important role in cardiovascular homeostasis by binding to V1a receptors on local somata and dendrites; and (v) the use of virally‐mediated optogenetics to dissect the role of OXT and AVP in the modulation of a wide variety of behaviours.