Genetic labeling of steroidogenic factor-1 (SF-1) neurons in mice reveals ventromedial nucleus of the hypothalamus (VMH) circuitry beginning at neurogenesis and development of a separate non-SF-1 neuronal cluster in the ventrolateral VMH.

Genetic labeling of steroidogenic factor-1 (SF-1) neurons in mice reveals ventromedial nucleus of the hypothalamus (VMH) circuitry beginning at neurogenesis and development of a separate non-SF-1 neuronal cluster in the ventrolateral VMH.
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DOI:
10.1002/cne.23226
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发表时间:
2013-04-15
影响因子:
2.5
通讯作者:
Ingraham, Holly A.
Ingraham, Holly A.
中科院分区:
医学3区
文献类型:
--
作者:
Cheung, Clement C.;Kurrasch, Deborah M.;Liang, Jenna K.;Ingraham, Holly A.

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下丘脑腹内侧核(VMH)影响多种生理反应。在这里,使用两种不同的,但互补的遗传示踪方法在小鼠中,我们描述了VMH传出投射的发展,标记类固醇生成因子-1(SF-1; NR 5A 1)。通过内源性Sf-1基因座表达的Tau绿色荧光蛋白(GFP)(Sf-1 TauGFP)或通过将转基因Sf 1:Cre驱动因子与GFP报告菌株(Z/EGSf 1:Cre)杂交,观察SF-1神经元。引人注目的是,VMH投射在胚胎(E)10.5早期就可见,此时几乎没有有丝分裂后SF 1神经元出生,这表明VMH回路的形成始于神经发生的开始。在E14.5,这两个报告细胞系的比较显示,在腹外侧VMH(VMHvl)中的SF 1阳性神经元持续存在于Z/EGSf 1:Cre胚胎中,但在Sf-1 TauGFP中几乎不存在。因此,尽管包括VMHvl的整个VMH共享共同的谱系,但VMHvl进一步分化成缺乏SF-1的神经元簇。在出生时,广泛的VMH预测广泛的大脑区域中观察到的两个小鼠报告线,匹配以及与以前发现的成年大鼠轴突顺行示踪剂注射。总之,我们的遗传追踪研究表明,VMH传出投射是高度保守的啮齿类动物和建立远早于以前的赞赏。此外,我们的研究结果意味着,在VMHvl神经元采用不同的命运在发展的早期,这可能是与此VMH亚区的独特的生理功能的基础。
The ventromedial nucleus of the hypothalamus (VMH) influences a wide variety of physiological responses. Here, using two distinct but complementary genetic tracing approaches in mice, we describe the development of VMH efferent projections, as marked by steroidogenic factor-1 (SF-1; NR5A1). SF-1 neurons were visualized by Tau-green fluorescent protein (GFP) expressed from the endogenous Sf-1 locus (Sf-1TauGFP) or by crossing the transgenic Sf1:Cre driver to a GFP reporter strain (Z/EGSf1:Cre). Strikingly, VMH projections were visible early, at embryonic (E) 10.5, when few postmitotic SF1 neurons have been born, suggesting that formation of VMH circuitry begins at the onset of neurogenesis. At E14.5, comparison of these two reporter lines revealed that SF1-positive neurons in the ventrolateral VMH (VMHvl) persist in Z/EGSf1:Cre embryos but are virtually absent in Sf-1TauGFP. Therefore, although the entire VMH including the VMHvl shares a common lineage, the VMHvl further differentiates into a neuronal cluster devoid of SF-1. At birth, extensive VMH projections to broad regions of the brain were observed in both mouse reporter lines, matching well with those previously discovered by injection of axonal anterograde tracers in adult rats. In summary, our genetic tracing studies show that VMH efferent projections are highly conserved in rodents and are established far earlier than previously appreciated. Moreover, our results imply that neurons in the VMHvl adopt a distinct fate early in development, which might underlie the unique physiological functions associated with this VMH subregion.
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