6月20號(hào),，《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《Tlx1/3 and Ptf1a control the expression of distinct sets of transmitter and peptide receptor genes in the developing dorsal spinal cord》,。該項(xiàng)工作是由研究生國(guó)禎、趙叢玲和黃夢(mèng)歸等在程樂(lè)平研究員的指導(dǎo)下共同完成的,。同期的 The Journal of Neuroscience 發(fā)表了題為“轉(zhuǎn)錄因子驅(qū)動(dòng)一些獨(dú)特的神經(jīng)環(huán)路相關(guān)蛋白的表達(dá)”（Transcription Factors Drive Distinct Neural Circuit Proteins）的評(píng)論,，對(duì)該項(xiàng)工作進(jìn)行了介紹。
弄清神經(jīng)遞質(zhì),、神經(jīng)肽及其受體在不同類型神經(jīng)元中的表達(dá)模式對(duì)于理解神經(jīng)系統(tǒng)中神經(jīng)環(huán)路的形成具有重要意義,。脊髓背角在軀體感覺(jué)信息從外周向大腦傳遞的過(guò)程中起重要作用。依照所使用的神經(jīng)遞質(zhì)的不同,，脊髓背角神經(jīng)元可分為興奮性的谷氨酸能神經(jīng)元與抑制性的γ-氨基丁酸能神經(jīng)元,。一些神經(jīng)肽也特異地表達(dá)在谷氨酸能神經(jīng)元或γ-氨基丁酸能神經(jīng)元中。我們及他人的工作曾報(bào)道一些轉(zhuǎn)錄因子決定脊髓背角谷氨酸能神經(jīng)元與γ-氨基丁酸能神經(jīng)元中神經(jīng)遞質(zhì)與神經(jīng)肽的表達(dá),。然而,，是否有一些神經(jīng)遞質(zhì)與神經(jīng)肽的受體特異地表達(dá)在谷氨酸能神經(jīng)元或γ-氨基丁酸能神經(jīng)元中，他們的表達(dá)受哪些基因調(diào)控,，目前的報(bào)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)多種神經(jīng)遞質(zhì)與神經(jīng)肽受體基因特異地表達(dá)在谷氨酸能神經(jīng)元中,。通過(guò)分析基因敲除小鼠的表型,，發(fā)現(xiàn)這些受體的表達(dá)依賴于決定谷氨酸能神經(jīng)元命運(yùn)的轉(zhuǎn)錄因子Tlx1/3。轉(zhuǎn)錄因子Lbx1與Ptf1a同時(shí)也對(duì)這些受體在谷氨酸能神經(jīng)元中的表達(dá)起調(diào)控作用,。進(jìn)一步實(shí)驗(yàn)表明,，多種神經(jīng)遞質(zhì)與神經(jīng)肽受體基因特異地表達(dá)在γ-氨基丁酸能神經(jīng)元中，它們的表達(dá)依賴于決定γ-氨基丁酸能神經(jīng)元命運(yùn)的轉(zhuǎn)錄因子Ptf1a,；轉(zhuǎn)錄因子Pax2與Tlx1/3也對(duì)這些受體基因在γ-氨基丁酸能神經(jīng)元中的表達(dá)起調(diào)控作用,。
該研究結(jié)果揭示了決定神經(jīng)元命運(yùn)的轉(zhuǎn)錄因子同時(shí)也決定了神經(jīng)元中特異表達(dá)的神經(jīng)遞質(zhì)與神經(jīng)肽受體的表達(dá)。這為認(rèn)識(shí)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,。
該工作得到了科技部及中科院項(xiàng)目的資助,。（生物谷Bioon.com）
doi:10.1523/JNEUROSCI.6301-11.2012
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Tlx1/3 and Ptf1a Control the Expression of Distinct Sets of Transmitter and Peptide Receptor Genes in the Developing Dorsal Spinal Cord
Zhen Guo1, Congling Zhao2, Menggui Huang2, Tianwen Huang2, Mingran Fan2, Zhiqin Xie1, Ying Chen1, Xiaolin Zhao2, Guannan Xia1, Junlan Geng2, and Leping Cheng2
Establishing the pattern of expression of transmitters and peptides as well as their receptors in different neuronal types is crucial for understanding the circuitry in various regions of the brain. Previous studies have demonstrated that the transmitter and peptide phenotypes in mouse dorsal spinal cord neurons are determined by the transcription factors Tlx1/3 and Ptf1a. Here we show that these transcription factors also determine the expression of two distinct sets of transmitter and peptide receptor genes in this region. We have screened the expression of 78 receptor genes in the spinal dorsal horn by in situ hybridization. We found that receptor genes Gabra1, Gabra5, Gabrb2, Gria3, Grin3a, Grin3b, Galr1, and Npy1r were preferentially expressed in Tlx3-expressing glutamatergic neurons and their derivatives, and deletion of Tlx1 and Tlx3 resulted in the loss of expression of these receptor genes. Furthermore, we obtained genetic evidence that Tlx3 uses distinct pathways to control the expression of receptor genes. We also found that receptor genes Grm3, Grm4, Grm5, Grik1, Grik2, Grik3, and Sstr2 were mainly expressed in Pax2-expressing GABAergic neurons in the spinal dorsal horn, and their expression in this region was abolished or markedly reduced in Ptf1a and Pax2 deletion mutant mice. Together, our studies indicate that Tlx1/3 and Ptf1a, the key transcription factors for fate determination of glutamatergic and GABAergic neurons in the dorsal spinal cord, are also responsible for controlling the expression of two distinct sets of transmitter and peptide receptor genes.
