Oliver Devyn, Alexander Kellianne, Francis Michael M
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA, USA.
J Exp Neurosci. 2018 Dec 2;12:1179069518816088. doi: 10.1177/1179069518816088. eCollection 2018.
The development of the nervous system requires precise outgrowth, extension, and wiring of both axons and dendrites to generate properly functioning neural circuits. The molecular mechanisms that shape neurite development, in particular dendritic development, remain incompletely understood. Dendrites are often highly branched and coated with actin-filled, thorny protrusions, called dendritic spines, that allow for increased numbers of synaptic contacts with neighboring neurons. Disruptions in dendritic spine development have been implicated in many neurological disorders such as autism, schizophrenia, and Alzheimer's disease. Although the development of dendritic spines is vital for cognitive function, understanding the mechanisms driving their outgrowth and stabilization remains a challenge. Our recent work identifies the presence of dendritic spine-like structures in the nematode and provides initial insights into mechanisms promoting spine outgrowth in this system. Specifically, we show that neurexin is a critical molecular component in directing the development of synaptic connections and promoting spine outgrowth. Our investigation provides important insights into the molecular machinery that sculpt synaptic connectivity, and continuing efforts in this system offer the potential for identifying new mechanisms governing both synaptic partner selection and dendritic spine outgrowth.
神经系统的发育需要轴突和树突精确地生长、延伸并形成连接，以生成功能正常的神经回路。塑造神经突发育，尤其是树突发育的分子机制仍未完全明晰。树突通常高度分支，并覆盖着充满肌动蛋白的棘状突起，即树突棘，这使得与相邻神经元的突触接触数量增加。树突棘发育的破坏与许多神经系统疾病有关，如自闭症、精神分裂症和阿尔茨海默病。尽管树突棘的发育对认知功能至关重要，但了解驱动其生长和稳定的机制仍然是一项挑战。我们最近的研究确定了线虫中存在类似树突棘的结构，并初步揭示了该系统中促进树突棘生长的机制。具体而言，我们发现神经连接蛋白是指导突触连接发育和促进树突棘生长的关键分子成分。我们的研究为塑造突触连接性的分子机制提供了重要见解，在该系统中持续开展的研究有可能发现控制突触伙伴选择和树突棘生长的新机制。
