Grueber Wesley B, Ye Bing, Yang Chung-Hui, Younger Susan, Borden Kelly, Jan Lily Y, Jan Yuh-Nung
Departments of Physiology and Biochemistry, University of California, San Francisco, Rock Hall, Room GD481, 1550 4th Street, San Francisco, CA 94143, USA.
Development. 2007 Jan;134(1):55-64. doi: 10.1242/dev.02666.
Neurons establish diverse dendritic morphologies during development, and a major challenge is to understand how these distinct developmental programs might relate to, and influence, neuronal function. Drosophila dendritic arborization (da) sensory neurons display class-specific dendritic morphology with extensive coverage of the body wall. To begin to build a basis for linking dendrite structure and function in this genetic system, we analyzed da neuron axon projections in embryonic and larval stages. We found that multiple parameters of axon morphology, including dorsoventral position, midline crossing and collateral branching, correlate with dendritic morphological class. We have identified a class-specific medial-lateral layering of axons in the central nervous system formed during embryonic development, which could allow different classes of da neurons to develop differential connectivity to second-order neurons. We have examined the effect of Robo family members on class-specific axon lamination, and have also taken a forward genetic approach to identify new genes involved in axon and dendrite development. For the latter, we screened the third chromosome at high resolution in vivo for mutations that affect class IV da neuron morphology. Several known loci, as well as putative novel mutations, were identified that contribute to sensory dendrite and/or axon patterning. This collection of mutants, together with anatomical data on dendrites and axons, should begin to permit studies of dendrite diversity in a combined developmental and functional context, and also provide a foundation for understanding shared and distinct mechanisms that control axon and dendrite morphology.
神经元在发育过程中形成多样的树突形态,而一个主要挑战是理解这些不同的发育程序如何与神经元功能相关并对其产生影响。果蝇树突分支(da)感觉神经元呈现出特定类别的树突形态,广泛覆盖体壁。为了在这个遗传系统中建立起将树突结构与功能联系起来的基础,我们分析了胚胎期和幼虫期da神经元的轴突投射。我们发现轴突形态的多个参数,包括背腹位置、中线交叉和侧支分支,与树突形态类别相关。我们确定了在胚胎发育过程中形成的中枢神经系统中轴突的特定类别内外分层,这可能使不同类别的da神经元与二阶神经元形成不同的连接。我们研究了Robo家族成员对特定类别轴突分层的影响,还采用正向遗传学方法来鉴定参与轴突和树突发育的新基因。对于后者,我们在体内对第三条染色体进行了高分辨率筛选,以寻找影响IV类da神经元形态的突变。我们鉴定出了几个已知位点以及可能的新突变,它们对感觉树突和/或轴突模式形成有贡献。这些突变体集合,连同关于树突和轴突的解剖学数据,应该开始能够在发育和功能相结合的背景下研究树突多样性,也为理解控制轴突和树突形态的共同和不同机制提供基础。