两篇Cell文章：解密神经发育的关键所在

　　生物通报道：10月10日公布在Cell杂志上的两篇论文分别描述了定位在细胞膜上的一种受体-配体复合物，这种复合物能指导树突的空间形态形成。

来自斯坦福大学的研究人员发表了题为“An Extracellular Adhesion Molecule Complex Patterns Dendritic Branching and Morphogenesis”的文章，发现了一种对于树突分支和形态形成至关重要的细胞外粘附分子复合物。

健康的树突形态是重复性神经环路发育的一个关键所在，然而关于模式复合物树突形态在细胞外的作用机制，至今科学家们了解的十分少。为此斯坦福大学的研究人员展开深入探索，利用线虫模型，发现了一种细胞外粘附分子复合物在这个过程中扮演了重要角色。

这种三重膜粘附分子受体-配体复合物是指导PVD树突空间限制性生长和分支的必要条件，配体复合SAX-7/L1CAM和MNR-1能作为周围皮下组织的固定点，DMA-1则作为PVD上的同源受体。

如果这个复合物出现突变，就会导致树突形成，稳定和组织过程出现极大的缺陷，SAX-7和MNR-1的异位表达也会产生DMA-1依赖性方式的预见性异常模式树突。这些体内和体外的实验表明，这三个分子相互作用，相互依存。

在另外一篇文章中，研究人员发现了一种在神经纤维分支过程中扮演关键角色的基因。他们指出在皮肤中可能有一个基因发挥作用“引导”附近树突分支，于是他们开始着手鉴别负责的基因。为了找到它，研究人员在线虫中诱导了随机突变，挑选出那些显示PVD树突分支缺陷的线虫，随后确定了造成分支缺陷的基因突变。

筛查结果揭示同一基因的4种突变引起了PVD 树突分支缺陷。研究人员证实，这一基因在皮肤中表达生成了一种胞外蛋白，在发育过程中触发了 PVD 树突正常分支。 PVD 神经元树突分支曾被描述与烛台相似，因此科学家们将这一基因命名为 mnr-1，将它的蛋白质命名为 Menorin 或 MNR-1。

进一步的研究发现，在皮肤中合成的Menorin 是促进 PVD 树突分支的必要而非充分条件。Menorin 蛋白似乎与 SAX-7/L1CAM 形成了一种复合物。SAX-7/L1CAM 是一种存在于线虫皮肤和其他部位的细胞粘附蛋白。研究人员发现的证据表明，当这两种蛋白构成的复合物被生长感觉树突上的受体分子 DMA-1 感知时，会随之发生树突分支。

原文摘要：

An Extracellular Adhesion Molecule Complex Patterns Dendritic Branching and Morphogenesis

Robust dendrite morphogenesis is a critical step in the development of reproducible neural circuits. However, little is known about the extracellular cues that pattern complex dendrite morphologies. In the model nematode Caenorhabditis elegans, the sensory neuron PVD establishes stereotypical, highly branched dendrite morphology. Here, we report the identification of a tripartite ligand-receptor complex of membrane adhesion molecules that is both necessary and sufficient to instruct spatially restricted growth and branching of PVD dendrites. The ligand complex SAX-7/L1CAM and MNR-1 function at defined locations in the surrounding hypodermal tissue, whereas DMA-1 acts as the cognate receptor on PVD. Mutations in this complex lead to dramatic defects in the formation, stabilization, and organization of the dendritic arbor. Ectopic expression of SAX-7 and MNR-1 generates a predictable, unnaturally patterned dendritic tree in a DMA-1-dependent manner. Both in vivo and in vitro experiments indicate that all three molecules are needed for interaction.

Skin-Derived Cues Control Arborization of Sensory Dendrites in Caenorhabditis elegans

Sensory dendrites depend on cues from their environment to pattern their growth and direct them toward their correct target tissues. Yet, little is known about dendrite-substrate interactions during dendrite morphogenesis. Here, we describe MNR-1/menorin, which is part of the conserved Fam151 family of proteins and is expressed in the skin to control the elaboration of menorah-like dendrites of mechanosensory neurons in Caenorhabditis elegans. We provide biochemical and genetic evidence that MNR-1 acts as a contact-dependent or short-range cue in concert with the neural cell adhesion molecule SAX-7/L1CAM in the skin and through the neuronal leucine-rich repeat transmembrane receptor DMA-1 on sensory dendrites. Our data describe an unknown pathway that provides spatial information from the skin substrate to pattern sensory dendrite development nonautonomously.