Regulation of neural stem cells by retinoic acid and Notch signalling in the regenerating axolotl spinal cord

点击翻译按钮获取中文摘要

The ability to regenerate a functional spinal cord is restricted to only a few vertebrate species, foremost among them tailed amphibians such as newts and salamanders, and some bony fish. The complex processes that underlie this ability in “regeneration-competent” species is still largely unknown. We are proposing to use the Mexican axolotl, a well-established regeneration-competent amphibian, to examine how spinal cord regeneration works. Based on our previous research, we plan to examine two communication pathways that coordinate interactions between cells during regeneration: the retinoic acid (RA) and Notch pathways. We will do this by using genetically modified “transgenic” axolotl larvae to identify and visualize the cellular sites of activity of multiple nuclear receptors for RA signaling in a key population of spinal cord cells the ependymoglial (EG) neural stem cells. We will bring to bear newly developed optogenetic' methods that will enable us to use light to regulate the communication events that occur in EG cells at various times during normal spinal cord regeneration. Importantly, our work will be the first to examine, at this level, how some intercellular communication networks are coordinated during spinal cord regeneration. All of this work will be performed by MSc and PhD students, who will receive valuable training in cutting edge methods in spinal cord research. Through the course of our work we will develop new research tools that will be shared with the spinal cord research community in Canada and abroad. We hope to make important new discoveries that can begin to unravel the complex signaling pathways that lead to regeneration competence in these species and which could shed light on why mammals have lost this ability during evolution.