如何創(chuàng)造出100億多個細胞,而每個細胞的職責又都不同?人類的大腦可以自然而然做到這一點。瑞典Linkping大學的研究人員現在已經向解決這個謎題邁出了第一步。
神經科學助理教授Mattias Alenius說:“了解神經元多樣化的機制,以及是如何讓它們擁有多樣性是必要的,,以便在未來能培養(yǎng)神經細胞和更換神經細胞,。他已將最新研究成果發(fā)表在本期PLoS Biology期刊上。
Alenius和實驗和臨床醫(yī)學部的研究小組從一個較小的角度尋求對這一關鍵問題的答案:果蠅的嗅覺系統(tǒng),。
我們不起眼的果蠅的嗅覺系統(tǒng)包含1200個嗅覺神經元(人類有600萬個),,共分為34組。每個神經元小組對一套特殊的氣味起反應,,因為每個神經元小組中所有的神經元只使用果蠅嗅覺中的一個受體,。總之,,受體提供果蠅辨別數以千計氣味的能力:一個嗅覺受體,,一組神經元,既簡單又復雜,。
Alenius和他的同事們首先通過研究果蠅的753個基因調控基因,,又稱為轉錄因子。他們已經鑒定確定了七個轉錄因子,,它們對建立嗅覺系統(tǒng)中所有34個神經元組都是必須的,。一個驚人的發(fā)現是大多數轉錄因子能同時執(zhí)行兩項任務:它們在激活感受氣味的受體表達時,而在同一時間能關閉同一細胞中其它的氣味受體,。
Alenius解釋說:“這研究對將來非常有幫助,,如果你想制造和培養(yǎng)構成我們大腦的成千上萬個神經細胞群之一的話。(生物谷:Bioon)
doi:10.1371/journal.pbio.1001280
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Combinatorial Activation and Repression by Seven Transcription Factors Specify Drosophila Odorant Receptor Expression
Shadi Jafari1, Liza Alkhori1, Alexander Schleiffer2, Anna Brochtrup3, Thomas Hummel3, Mattias Alenius1*
The mechanism that specifies olfactory sensory neurons to express only one odorant receptor (OR) from a large repertoire is critical for odor discrimination but poorly understood. Here, we describe the first comprehensive analysis of OR expression regulation in Drosophila. A systematic, RNAi-mediated knock down of most of the predicted transcription factors identified an essential function of acj6, E93, Fer1, onecut, sim, xbp1, and zf30c in the regulation of more than 30 ORs. These regulatory factors are differentially expressed in antennal sensory neuron classes and specifically required for the adult expression of ORs. A systematic analysis reveals not only that combinations of these seven factors are necessary for receptor gene expression but also a prominent role for transcriptional repression in preventing ectopic receptor expression. Such regulation is supported by bioinformatics and OR promoter analyses, which uncovered a common promoter structure with distal repressive and proximal activating regions. Thus, our data provide insight into how combinatorial activation and repression can allow a small number of transcription factors to specify a large repertoire of neuron classes in the olfactory system.