Molecular and behavioral profiling of Dbx1-derived neurons in the arcuate, lateral and ventromedial hypothalamic nuclei.
Molecular and behavioral profiling of Dbx1-derived neurons in the arcuate, lateral and ventromedial hypothalamic nuclei.
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DOI：
10.1186/s13064-016-0067-9
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发表时间：
2016-05-21
影响因子：
3.6
通讯作者：
Corbin JG
中科院分区：
文献类型：
--
作者：
Sokolowski K;Tran T;Esumi S;Kamal Y;Oboti L;Lischinsky J;Goodrich M;Lam A;Carter M;Nakagawa Y;Corbin JG
下丘脑中的神经元在学习和先天行为期间起调节动物状态的作用，并且下丘脑发育的改变可能导致诸如焦虑、抑郁或肥胖的病理状况。尽管下丘脑发育和功能的许多研究，胚胎发育和先天行为之间的联系仍然没有探索。在这里，专注于胚胎表达的同源结构域基因发育脑同源框1（Dbx 1），我们探讨了胚胎谱系，出生后的神经元身份和谱系特异性反应先天线索之间的关系。我们发现Dbx 1在多个发育中的下丘脑亚区广泛表达。使用标准和诱导的命运映射来追踪Dbx 1衍生的神经元，我们确定了它们对下丘脑核团中特定神经元亚型的贡献，并进一步映射了它们对一系列明确的先天行为的激活模式。Dbx 1源性神经元占据多个出生后的下丘脑核团，包括外侧下丘脑（LH），弓状核（Arc）和腹内侧下丘脑（VMH）。在这些细胞核内，Dbx 1+祖细胞产生大比例的Pmch-、Nesfatin-、Cart-、Hcrt-、Agrp-和ERα-表达神经元群体，以及较小程度的Pomc-、TH-和芳香化酶-表达群体。诱导性命运定位揭示了Dbx 1衍生的LH和Arc群体发育的不同时间窗口，Arc中的Agrp+和Cart+群体出现较早（E7.5-E9.5），而LH中的Pmch+和Hcrt+群体来自表达Dbx 1的祖细胞（E9.5-E11.5）。此外，c-Fos标记显示，Dbx 1衍生的细胞在男性和女性的LH，Arc和VMH的交配和侵略过程中作出反应。相比之下，弧和LH中的Dbx 1谱系细胞具有更广泛的行为调节，包括对禁食和捕食者气味线索的反应。我们定义了一个新的命运地图的下丘脑Dbx 1在下丘脑祖细胞区的表达。我们表明，在一个时间调节的方式，Dbx 1衍生的神经元有助于分子不同的神经元群体中的LH，弧和VMH已牵连在各种下丘脑驱动的行为。与此一致的是，LH、Arc和VMH中的Dbx 1衍生神经元在应激和其他先天行为反应期间被激活，暗示它们参与了这些不同的行为。本文的在线版本（doi：10.1186/s13064-016-0067-9）包含补充材料，可供授权用户使用。
Neurons in the hypothalamus function to regulate the state of the animal during both learned and innate behaviors, and alterations in hypothalamic development may contribute to pathological conditions such as anxiety, depression or obesity. Despite many studies of hypothalamic development and function, the link between embryonic development and innate behaviors remains unexplored. Here, focusing on the embryonically expressed homeodomain-containing gene Developing Brain Homeobox 1 (Dbx1), we explored the relationship between embryonic lineage, post-natal neuronal identity and lineage-specific responses to innate cues. We found that Dbx1 is widely expressed across multiple developing hypothalamic subdomains. Using standard and inducible fate-mapping to trace the Dbx1-derived neurons, we identified their contribution to specific neuronal subtypes across hypothalamic nuclei and further mapped their activation patterns in response to a series of well-defined innate behaviors. Dbx1-derived neurons occupy multiple postnatal hypothalamic nuclei including the lateral hypothalamus (LH), arcuate nucleus (Arc) and the ventral medial hypothalamus (VMH). Within these nuclei, Dbx1+ progenitors generate a large proportion of the Pmch-, Nesfatin-, Cart-, Hcrt-, Agrp- and ERα-expressing neuronal populations, and to a lesser extent the Pomc-, TH- and Aromatase-expressing populations. Inducible fate-mapping reveals distinct temporal windows for development of the Dbx1-derived LH and Arc populations, with Agrp+ and Cart+ populations in the Arc arising early (E7.5-E9.5), while Pmch+ and Hcrt+ populations in the LH derived from progenitors expressing Dbx1 later (E9.5-E11.5). Moreover, as revealed by c-Fos labeling, Dbx1-derived cells in male and female LH, Arc and VMH are responsive during mating and aggression. In contrast, Dbx1-lineage cells in the Arc and LH have a broader behavioral tuning, which includes responding to fasting and predator odor cues. We define a novel fate map of the hypothalamus with respect to Dbx1 expression in hypothalamic progenitor zones. We demonstrate that in a temporally regulated manner, Dbx1-derived neurons contribute to molecularly distinct neuronal populations in the LH, Arc and VMH that have been implicated in a variety of hypothalamic-driven behaviors. Consistent with this, Dbx1-derived neurons in the LH, Arc and VMH are activated during stress and other innate behavioral responses, implicating their involvement in these diverse behaviors. The online version of this article (doi:10.1186/s13064-016-0067-9) contains supplementary material, which is available to authorized users.