LAUSR

repair damaged sites remain elusive. To develop more effective treatments we need to understand the molecular mechanisms that produce functional spinal circuits. In addition, to fully understand the genetic basis of CNS functions and disorders we need to be able to connect individual genes with specific circuit properties and behaviors. This is a difficult task unless we understand how specific genes regulate the development of neuronal circuitry and hence enable particular behavioral repertoires. A particularly tractable model system for this research is zebrafish spinal circuitry. Specification of distinct neurons with particular functional properties is a crucial step in circuit formation. Interneurons constitute most of the neurons in the CNS and function in almost all neuronal circuits. However, there are significant gaps in our knowledge of how spinal interneurons with specific functions develop. All of the evidence so far, suggests that interneuron properties are determined by transcription factors (TFs) that these cells express as they start to differentiate. However, in many cases, it is still unclear which TFs specify particular properties. To address these critical gaps in knowledge we have expressionprofiled different zebrafish spinal interneurons and identified TFs that are strong candidates for specifying particular interneuron properties. We are currently concentrating on TFs that specify neurotransmitter properties. For example, we have shown that Pax2 and Pax8 are required for inhibitory fates of many spinal neurons and Evx1, Evx2 and Lmx1b are required for excitatory fates of V0v neurons. We have also identified several transcription factors that may be part of a common genetic pathway for specifying excitatory fates of spinal neurons, acting downstream of Evx1/2 in V0v neurons and downstream of other cell-type specific TFs in different excitatory neurons.