Genetic programs activated by proneural proteins in the developing Drosophila PNS

Genetic programs activated by proneural proteins in the developing Drosophila PNS
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DOI:
10.1016/j.devcel.2005.01.020
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发表时间:
2005-03-01
期刊:
影响因子:
11.8
通讯作者:
Posakony, JW
Posakony, JW
中科院分区:
生物学1区
文献类型:
--
作者:
Reeves, N;Posakony, JW

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神经发生依赖于一个家族的原神经转录激活蛋白,但这些因素的“原神经”功能知之甚少,部分原因是因为他们激活的基因,直接或间接的合奏,还没有被系统地确定。我们已经在果蝇中对这个问题采取了直接的方法。使用活化的细胞分选来回收纯化的细胞群,所述细胞群包含周围神经系统(PNS)的感觉器官前体所产生的“前神经簇”。全基因组微阵列分析和原位杂交,然后被用来确定和验证一组基因,优先表达在前神经丛细胞。这组基因编码的蛋白质具有多种隐含功能,对两个候选基因的功能丧失分析表明,它们确实是正常PNS发育所需的。生物信息学和报告基因的研究进一步阐明了顺式调控代码,直接在原神经簇的表达。
Neurogenesis depends on a family of proneural transcriptional activator proteins, but the "proneural" function of these factors is poorly understood, in part because the ensemble of genes they activate, directly or indirectly, has not been identified systematically. We have taken a direct approach to this problem in Drosophila. Fluorescence-activated cell sorting was used to recover a purified population of the cells that comprise the "proneural clusters" from which sensory organ precursors of the peripheral nervous system (PNS) arise. Whole-genome microarray analysis and in situ hybridization was then used to identify and verify a set of genes that are preferentially expressed in proneural cluster cells. Genes in this set encode proteins with a diverse array of implied functions, and loss-of-function analysis of two candidate genes shows that they are indeed required for normal PNS development. Bioinformatic and reporter gene studies further illuminate the cis-regulatory codes that direct expression in proneural clusters.