Department of Biology, University of Washington, Seattle, WA 98195, USA.
Center for Molecular Neurobiology, Hamburg D-20251, Germany.
Development. 2014 Jul;141(13):2657-68. doi: 10.1242/dev.107573. Epub 2014 Jun 12.
As animals grow, many early born structures grow by cell expansion rather than cell addition; thus growth of distinct structures must be coordinated to maintain proportionality. This phenomenon is particularly widespread in the nervous system, with dendrite arbors of many neurons expanding in concert with their substrate to sustain connectivity and maintain receptive field coverage as animals grow. After rapidly growing to establish body wall coverage, dendrites of Drosophila class IV dendrite arborization (C4da) neurons grow synchronously with their substrate, the body wall epithelium, providing a system to study how proportionality is maintained during animal growth. Here, we show that the microRNA bantam (ban) ensures coordinated growth of C4da dendrites and the epithelium through regulation of epithelial endoreplication, a modified cell cycle that entails genome amplification without cell division. In Drosophila larvae, epithelial endoreplication leads to progressive changes in dendrite-extracellular matrix (ECM) and dendrite-epithelium contacts, coupling dendrite/substrate expansion and restricting dendrite growth beyond established boundaries. Moreover, changes in epithelial expression of cell adhesion molecules, including the beta-integrin myospheroid (mys), accompany this developmental transition. Finally, endoreplication and the accompanying changes in epithelial mys expression are required to constrain late-stage dendrite growth and structural plasticity. Hence, modulating epithelium-ECM attachment probably influences substrate permissivity for dendrite growth and contributes to the dendrite-substrate coupling that ensures proportional expansion of the two cell types.
随着动物的生长,许多早期出生的结构通过细胞扩张而不是细胞增加来生长;因此,不同结构的生长必须协调一致,以保持比例性。这种现象在神经系统中尤为普遍,许多神经元的树突分支与它们的基质一起扩张,以维持连接性并保持动物生长过程中的感受野覆盖。在快速生长以建立体壁覆盖之后,果蝇第四类树突分支(C4da)神经元的树突与它们的基质,即体壁上皮,同步生长,为研究动物生长过程中如何保持比例性提供了一个系统。在这里,我们表明,微小 RNA bantam(ban)通过调节上皮内复制来确保 C4da 树突和上皮的协调生长,上皮内复制是一种经过修饰的细胞周期,涉及基因组扩增而不进行细胞分裂。在果蝇幼虫中,上皮内复制导致树突-细胞外基质(ECM)和树突-上皮接触的渐进变化,将树突/基质扩张与限制树突生长到已建立的边界之外联系起来。此外,上皮细胞黏附分子的表达变化,包括β-整合素 myospheroid(mys),伴随着这种发育转变。最后,内复制和上皮 mys 表达的伴随变化是限制晚期树突生长和结构可塑性所必需的。因此,调节上皮-ECM 附着可能会影响基质对树突生长的允许性,并有助于确保两种细胞类型比例扩张的树突-基质耦联。