Determining the Transcription Factor Code that Specifies CiA Interneurons

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Our ability to treat people with neurological disorders or spinal cord injuries is currently constrained by our limited understanding of how the central nervous system develops and functions. In particular, we know very little about how different types of nerve cells (neurons) are made. In this research grant we aim to determine which genes are involved in making a specific population of spinal cord neurons, called CiA interneurons, in zebrafish embryos. The spinal cord is the part of the nervous system inside the vertebral column in the back and it is responsible for controlling body movements and for receiving information about pain, touch and heat from the body and limbs. This is why people with damaged spinal cords are often paralysed. For the neuronal circuitry of the spinal cord to function, specific neurons need to develop in particular positions and make appropriate connections with each other. We still know very little about how these processes are regulated. Excitingly, we can now exploit the cell biology and genetics of zebrafish embryos to identify specific neurons in live embryos and determine how their positions, cell shapes, neuronal connections and functions are specified. We have identified several regulatory genes that we think are important for instructing CiA interneurons to acquire their particular characteristics (e.g. shape of the nerve cell, what other nerve cells it communicates with and the chemicals that it uses to communicate). These genes encode for regulatory proteins called transcription factors which are responsible for turning other genes on and off. In this project, we will test the individual and combined functions of these transcription factors in making CiA interneurons. CiA interneurons are made and function in very similar ways to a specific population of interneurons in mammals (V1 cells), so our findings should also be relevant to humans. This research is important because the more we learn about how different neurons are made, the more likely we are to be able to develop treatments for neurological diseases and/or spinal cord injuries. For example, once we know which genes specify particular neurons we can use this information to instruct stem cells to grow into those neurons.