Ou Yimiao, Chwalla Barbara, Landgraf Matthias, van Meyel Donald J
Centre for Research in Neuroscience, McGill University, Cedar Ave, Montreal, QC, H3G 1A4, Canada.
Neural Dev. 2008 Jul 10;3:16. doi: 10.1186/1749-8104-3-16.
Developing neurons form dendritic trees with cell type-specific patterns of growth, branching and targeting. Dendrites of Drosophila peripheral sensory neurons have emerged as a premier genetic model, though the molecular mechanisms that underlie and regulate their morphogenesis remain incompletely understood. Still less is known about this process in central neurons and the extent to which central and peripheral dendrites share common organisational principles and molecular features. To address these issues, we have carried out two comparable gain-of-function screens for genes that influence dendrite morphologies in peripheral dendritic arborisation (da) neurons and central RP2 motor neurons.
We found 35 unique loci that influenced da neuron dendrites, including five previously shown as required for da dendrite patterning. Several phenotypes were class-specific and many resembled those of known mutants, suggesting that genes identified in this study may converge with and extend known molecular pathways for dendrite development in da neurons. The second screen used a novel technique for cell-autonomous gene misexpression in RP2 motor neurons. We found 51 unique loci affecting RP2 dendrite morphology, 84% expressed in the central nervous system. The phenotypic classes from both screens demonstrate that gene misexpression can affect specific aspects of dendritic development, such as growth, branching and targeting. We demonstrate that these processes are genetically separable. Targeting phenotypes were specific to the RP2 screen, and we propose that dendrites in the central nervous system are targeted to territories defined by Cartesian co-ordinates along the antero-posterior and the medio-lateral axes of the central neuropile. Comparisons between the screens suggest that the dendrites of peripheral da and central RP2 neurons are shaped by regulatory programs that only partially overlap. We focused on one common candidate pathway controlled by the ecdysone receptor, and found that it promotes branching and growth of developing da neuron dendrites, but a role in RP2 dendrite development during embryonic and early larval stages was not apparent.
We identified commonalities (for example, growth and branching) and distinctions (for example, targeting and ecdysone response) in the molecular and organizational framework that underlies dendrite development of peripheral and central neurons.
发育中的神经元形成具有细胞类型特异性生长、分支和靶向模式的树突状树。果蝇外周感觉神经元的树突已成为一个重要的遗传模型，但其形态发生的潜在分子机制仍未完全了解。对于中枢神经元中的这一过程以及中枢和外周树突在多大程度上共享共同的组织原则和分子特征，人们了解得更少。为了解决这些问题，我们针对影响外周树突状分支（da）神经元和中枢RP2运动神经元树突形态的基因进行了两项可比的功能获得性筛选。
我们发现了35个影响da神经元树突的独特基因座，其中包括5个先前已证明对da树突模式形成必不可少的基因座。几种表型具有类别特异性，许多类似于已知突变体的表型，这表明本研究中鉴定的基因可能与da神经元中已知的树突发育分子途径汇聚并扩展这些途径。第二项筛选使用了一种用于RP2运动神经元细胞自主基因错误表达的新技术。我们发现了51个影响RP2树突形态的独特基因座，其中84%在中枢神经系统中表达。两项筛选的表型类别表明，基因错误表达可影响树突发育的特定方面，如生长、分支和靶向。我们证明这些过程在遗传上是可分离的。靶向表型是RP2筛选所特有的，我们提出中枢神经系统中的树突靶向于沿着中枢神经纤维前后轴和中外侧轴由笛卡尔坐标定义的区域。两项筛选之间的比较表明，外周da神经元和中枢RP2神经元的树突是由仅部分重叠的调控程序塑造的。我们聚焦于由蜕皮激素受体控制的一条共同候选途径，发现它促进发育中的da神经元树突的分支和生长，但在胚胎期和幼虫早期对RP2树突发育的作用并不明显。
我们确定了外周和中枢神经元树突发育的分子和组织框架中的共性（如生长和分支）和差异（如靶向和蜕皮激素反应）。
