Spletter Maria Lynn, Liu Jian, Liu Justin, Su Helen, Giniger Edward, Komiyama Takaki, Quake Stephen, Luo Liqun
Howard Hughes Medical Institute, Department of Biological Sciences, Stanford University, Stanford, California 94305, USA.
Neural Dev. 2007 Jul 16;2:14. doi: 10.1186/1749-8104-2-14.
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.
神经回路的精确连接可由基因编程来确定。在果蝇嗅觉系统中，投射神经元（PNs）依据谱系和出生顺序将树突发送至触角叶（AL）中的单个神经小球，并将轴突以刻板的终止方式发送至更高阶的嗅觉中枢。这些决定可能由一种PN内在的转录密码所确定，该密码调节细胞表面分子的表达以指导线路特异性。
我们发现，缺乏纵向蛋白（lola）（其编码一种具有20种预测剪接异构体的BTB -锌指转录因子）的缺失会导致所有PN谱系的轴突和树突出现线路缺陷。RNA原位杂交和定量RT - PCR表明，即便不是全部，大多数lola异构体在所有PN中均有表达，但不同异构体的表达水平差异很大。单个lola异构体的过表达无法挽救lola缺失的表型，反而会导致额外的表型。lola的缺失还会导致Gal4驱动蛋白在多种细胞类型中异位表达，以及腹侧PN中转录因子基因lim1表达的丧失。
我们的结果表明，lola是大多数PN类别的轴突和树突线路形成所必需的，并提示需要其分子多样性。lola基因敲除克隆中Gal4驱动蛋白的表达模式变化意味着，lola通常会在AL周围的一部分细胞中抑制这些调控元件的表达。我们提出，Lola作为一种通用转录因子，调节多个基因的表达，最终控制PN的特性和线路特异性。
