NOVEL EXTRACELLULAR PROTEINS IN AXON GUIDANCE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们神经系统的细胞之间相隔很远，必须通过能够传递电信号或化学信号的线路相互连接。单个纤维被称为轴突，在早期胚胎中，它们必须通过很长的距离连接神经系统。细胞通过其表面上的蛋白质（称为受体）来感知环境，这些蛋白质结合环境中的信号。目前已知的轴突信号和受体很少。一类是Netrin蛋白家族，它刺激发育中的脊髓中生长的神经以及包括血管在内的其他细胞类型。通过基因筛选，我们已经确定了Netrin蛋白的一种新受体，即唐氏综合征细胞粘附分子（Dscam）。在唐氏综合症患者中，有一个额外的21号染色体拷贝。虽然21号染色体上有几百个基因，但只有少数基因被认为是造成大多数症状的原因。其中一个基因是Dscam，一种细胞粘附分子，它允许细胞相互粘附。Kidd博士的工作表明，Dscam作为Netrin受体发挥作用，引导神经和细胞迁移。Dscam似乎也是一种受体，用于尚未确定的在发育中的神经系统中起作用的线索。这增加了我们对脊髓和大脑如何形成的理解，以及对脊髓损伤的影响，以及其他影响神经和血管的疾病，如糖尿病。Dscam作为细胞粘附分子和受体的功能的知识应该允许更好地了解唐氏综合征表型如何发展，包括患者中常见的先天性心脏病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The cells of our nervous system are separated by large distances and must be connected to one another by wiring capable of carrying electrical or chemical signals. The individual fibers are known as axons, and in the early embryo they have to navigate large distances to connect up the nervous system. Cells sense their environment through proteins, known as receptors, on their surfaces that bind signals in their environment. Few signals and receptors for axons are currently known. One class is the Netrin protein family that stimulates growing nerves in the developing spinal cord, as well as other cell types including blood vessels. Through genetic screens, we have identified a novel receptor for Netrin proteins, the Down Syndrome Cell Adhesion Molecule (Dscam). In Down syndrome patients, there is an extra copy of chromosome 21. Although there are several hundred genes on chromosome 21, only a few of those genes are thought to be responsible for the majority of the symptoms. One of these genes is Dscam, a cell adhesion molecule, which allows cells to stick to one another. Dr. Kidd's work has shown that Dscam functions as a Netrin receptor to guide both nerves and cells as they migrate. Dscam also appears to be a receptor for yet to be identified cues that function in the developing nervous system. This adds to our understanding of how spinal cords and brains form, as well as having implications for spinal cord injury, as well as other conditions that impact both nerves and blood vessels such as diabetes. Knowledge that Dscam functions as both a cell adhesion molecule and as a receptor should allow for a greater understanding of how the Down Syndrome phenotype develops, including the congenital heart disease frequently seen in patients.