6月26日,，《神經(jīng)科學(xué)雜志》(The Journal of Neuroscience) 發(fā)表了中科院上海生科院神經(jīng)所神經(jīng)發(fā)育及其調(diào)控機(jī)理研究組的論文《Tlx3 Controls Cholinergic Transmitter and Peptide Phenotypes in a Subset of Prenatal Sympathetic Neurons》,。該項工作由研究生黃天文、胡佳等在程樂平研究員的指導(dǎo)下共同完成,。
交感神經(jīng)為自主神經(jīng)系統(tǒng)的重要組成部分,，它廣泛參與不同生理條件下動物體內(nèi)環(huán)境的穩(wěn)定。交感神經(jīng)節(jié)中主要存在兩類神經(jīng)元：去甲腎上腺素能神經(jīng)元及乙酰膽堿能神經(jīng)元,。闡明這兩類神經(jīng)元如何產(chǎn)生是發(fā)育神經(jīng)生物學(xué)中的重要問題,。目前已有工作發(fā)現(xiàn)一些轉(zhuǎn)錄因子調(diào)控交感神經(jīng)節(jié)中去甲腎上腺素能神經(jīng)元的發(fā)生。關(guān)于交感神經(jīng)節(jié)中乙酰膽堿能神經(jīng)元的產(chǎn)生,，經(jīng)典的理論認(rèn)為,，支配汗腺與骨膜的乙酰膽堿能神經(jīng)元由去甲腎上腺素能神經(jīng)元轉(zhuǎn)變而來。去甲腎上腺素能神經(jīng)元接觸到靶器官汗腺與骨膜后,，在這些靶器官分泌的細(xì)胞因子的作用下喪失自身功能,，同時轉(zhuǎn)變?yōu)橐阴Ｄ憠A能神經(jīng)元。交感神經(jīng)節(jié)中除了存在出生后由去甲腎上腺素能神經(jīng)元轉(zhuǎn)變來的乙酰膽堿能神經(jīng)元外,，近年來人們發(fā)現(xiàn)胚胎期交感神經(jīng)節(jié)中也存在乙酰膽堿能神經(jīng)元,。胚胎期交感神經(jīng)節(jié)中乙酰膽堿能神經(jīng)元如何產(chǎn)生，目前的報道還很少,。
利用原位雜交及免疫組化染色技術(shù),，作者發(fā)現(xiàn)胚胎發(fā)育過程中轉(zhuǎn)錄因子Tlx3逐漸在交感神經(jīng)節(jié)乙酰膽堿能神經(jīng)元中富集。通過分析基因敲除小鼠的表型,，發(fā)現(xiàn)Tlx3參與維持胚胎期乙酰膽堿能神經(jīng)元的遞質(zhì)表型,，同時控制乙酰膽堿能神經(jīng)元中血管活性腸肽（VIP）與生長抑素（SOM）等神經(jīng)肽的表達(dá)。Tlx3并不決定胚胎期去甲腎上腺素能神經(jīng)元的發(fā)生,。進(jìn)一步實驗表明,，Tlx3調(diào)控乙酰膽堿能神經(jīng)元中膠質(zhì)細(xì)胞源性神經(jīng)營養(yǎng)因子（GFNF）家族輔助受體Ret的表達(dá),，而且Ret參與維持神經(jīng)肽VIP和SOM在乙酰膽堿能神經(jīng)元中的表達(dá)。
該研究結(jié)果首次揭示了轉(zhuǎn)錄因子決定胚胎期交感神經(jīng)節(jié)中乙酰膽堿能神經(jīng)元的遞質(zhì)表型,。這為認(rèn)識神經(jīng)元的發(fā)育調(diào)控及神經(jīng)環(huán)路的形成機(jī)制提供了新的視角,。（神經(jīng)所）
轉(zhuǎn)錄因子Tlx3調(diào)控交感神經(jīng)節(jié)中乙酰膽堿能神經(jīng)元的發(fā)育
生物谷推薦的英文摘要
J Neurosci. doi: 10.1523/JNEUROSCI.0192-13.2013
Huang T, Hu J, Wang B, Nie Y, Geng J, Cheng L.
Tlx3 controls cholinergic transmitter and Peptide phenotypes in a subset of prenatal sympathetic neurons
The embryonic sympathetic nervous system consists of predominantly noradrenergic neurons and a very small population of cholinergic neurons. Postnatal development further allows target-dependent switch of a subset of noradrenergic neurons into cholinergic phenotype. How embryonic cholinergic neurons are specified at the prenatal stages remains largely unknown. In this study, we found that the expression of transcription factor Tlx3 was progressively restricted to a small population of embryonic sympathetic neurons in mice. Immunostaining for vesicular acetylcholine transporter (VAChT) showed that Tlx3 was highly expressed in cholinergic neurons at the late embryonic stage E18.5. Deletion of Tlx3 resulted in the loss of Vacht expression at E18.5 but not E12.5. By contrast, Tlx3 was required for expression of the cholinergic peptide vasoactive intestinal polypeptide (VIP), and somatostatin (SOM) at both E12.5 and E18.5. Furthermore, we found that, at E18.5 these putative cholinergic neurons expressed glial cell line-derived neurotrophic factor family coreceptor Ret but not tyrosine hydroxylase (Ret(+)/TH(-)). Deletion of Tlx3 also resulted in disappearance of high-level Ret expression. Last, unlike Tlx3, Ret was required for the expression of VIP and SOM at E18.5 but not E12.5. Together, these results indicate that transcription factor Tlx3 is required for the acquisition of cholinergic phenotype at the late embryonic stage as well as the expression and maintenance of cholinergic peptides VIP and SOM throughout prenatal development of mouse sympathetic neurons.
