如何創(chuàng)造出100億多個(gè)細(xì)胞,，而每個(gè)細(xì)胞的職責(zé)又都不同,？人類的大腦可以自然而然做到這一點(diǎn),。瑞典Linkping大學(xué)的研究人員現(xiàn)在已經(jīng)向解決這個(gè)謎題邁出了第一步。
神經(jīng)科學(xué)助理教授Mattias Alenius說：“了解神經(jīng)元多樣化的機(jī)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(jīng)細(xì)胞和更換神經(jīng)細(xì)胞。他已將最新研究成果發(fā)表在本期PLoS Biology期刊上,。
Alenius和實(shí)驗(yàn)和臨床醫(yī)學(xué)部的研究小組從一個(gè)較小的角度尋求對(duì)這一關(guān)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(gè)嗅覺神經(jīng)元（人類有600萬個(gè)），共分為34組,。每個(gè)神經(jīng)元小組對(duì)一套特殊的氣味起反應(yīng),，因?yàn)槊總€(gè)神經(jīng)元小組中所有的神經(jīng)元只使用果蠅嗅覺中的一個(gè)受體?？傊?，受體提供果蠅辨別數(shù)以千計(jì)氣味的能力：一個(gè)嗅覺受體，一組神經(jīng)元,，既簡單又復(fù)雜,。
Alenius和他的同事們首先通過研究果蠅的753個(gè)基因調(diào)控基因，又稱為轉(zhuǎn)錄因子,。他們已經(jīng)鑒定確定了七個(gè)轉(zhuǎn)錄因子,，它們對(duì)建立嗅覺系統(tǒng)中所有34個(gè)神經(jīng)元組都是必須的。一個(gè)驚人的發(fā)現(xiàn)是大多數(shù)轉(zhuǎn)錄因子能同時(shí)執(zhí)行兩項(xiàng)任務(wù)：它們?cè)诩せ罡惺軞馕兜氖荏w表達(dá)時(shí),，而在同一時(shí)間能關(guān)閉同一細(xì)胞中其它的氣味受體,。
Alenius解釋說：“這研究對(duì)將來非常有幫助，如果你想制造和培養(yǎng)構(gòu)成我們大腦的成千上萬個(gè)神經(jīng)細(xì)胞群之一的話,。（生物谷：Bioon）
doi:10.1371/journal.pbio.1001280
PMC:
PMID:
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.
