Lola regulates Drosophila olfactory projection neuron identity and targeting specificity.
Lola regulates Drosophila olfactory projection neuron identity and targeting specificity.
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Lola调节果蝇嗅觉投影神经元的身份和靶向特异性。
DOI：
10.1186/1749-8104-2-14
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发表时间：
2007-07-16
影响因子：
3.6
通讯作者：
Luo L
中科院分区：
文献类型：
--
作者：
Spletter ML;Liu J;Liu J;Su H;Giniger E;Komiyama T;Quake S;Luo L
神经回路的精确连接可以通过遗传编程来指定。在果蝇嗅觉系统中，投射神经元（PN）根据谱系和出生顺序将树突发送到天线叶（AL）中的单个肾小球，并将具有定型终止的轴突发送到高级嗅觉中心。这些决定可能是由PN内在转录密码指定的，该密码调节细胞表面分子的表达以指示布线特异性。我们发现，丢失的神经元缺乏（lola），它编码的BTB-Zn-finger转录因子与20个预测的剪接异构体，导致布线缺陷的轴突和树突的所有谱系的PN。RNA原位杂交和定量RT-PCR表明，大多数（如果不是所有）萝拉亚型在所有PN中表达，但不同的亚型表达水平差异很大。单个lola异构体的过表达不能挽救lola无效表型，并导致额外的表型。lola的缺失还导致Gal 4驱动因子在多种细胞类型中的异位表达以及腹侧PN中转录因子基因lim 1表达的缺失。我们的研究结果表明，萝拉是需要布线的轴突和树突的PN类，并建议需要其分子的多样性。在萝拉-/-克隆Gal 4驱动程序的表达模式的变化意味着，萝拉通常抑制这些调控元件的表达在AL周围的细胞的一个子集。我们建议，萝拉作为一个通用的转录因子，调节多个基因的表达，最终控制PN身份和布线特异性。
Precise connections of neural circuits can be specified by genetic programming. In the Drosophila olfactory system, projection neurons (PNs) send dendrites to single glomeruli in the antenna lobe (AL) based upon lineage and birth order and send axons with stereotyped terminations to higher olfactory centers. These decisions are likely specified by a PN-intrinsic transcriptional code that regulates the expression of cell-surface molecules to instruct wiring specificity. We find that the loss of longitudinals lacking (lola), which encodes a BTB-Zn-finger transcription factor with 20 predicted splice isoforms, results in wiring defects in both axons and dendrites of all lineages of PNs. RNA in situ hybridization and quantitative RT-PCR suggest that most if not all lola isoforms are expressed in all PNs, but different isoforms are expressed at widely varying levels. Overexpression of individual lola isoforms fails to rescue the lola null phenotypes and causes additional phenotypes. Loss of lola also results in ectopic expression of Gal4 drivers in multiple cell types and in the loss of transcription factor gene lim1 expression in ventral PNs. Our results indicate that lola is required for wiring of axons and dendrites of most PN classes, and suggest a need for its molecular diversity. Expression pattern changes of Gal4 drivers in lola-/- clones imply that lola normally represses the expression of these regulatory elements in a subset of the cells surrounding the AL. We propose that Lola functions as a general transcription factor that regulates the expression of multiple genes ultimately controlling PN identity and wiring specificity.
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影响因子：
7.4
作者：
Liu, J;Hansen, C;Quake, SR
通讯作者：
Quake, SR
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