Okazaki Institute for Integrative Biology

RESEARCH THEMES

1) Development and function of spinal locomotor circuits in zebrafish.
Recent molecular genetic studies have implicated a number of transcription factors in the specification of different interneurons. Investigating how interneurons develop and function in amniotes, however, is not trivial due to enormous complexity of their spinal circuits. In contrast, zebrafish spinal circuits are much simpler with less number of distinct classes of neurons, making it more feasible to address this issue. We have set to define the morphology and functional properties of spinal neurons that express a particular transcription factor. Methodologically, the core of our approach is to visualize transcription factor positive cells by making transgenic zebrafish that express fluorescent proteins in these cells. The transparency of embryos and larvae greatly facilitate morphological and physiological analyses of the labeled neurons. We have made a number of transgenic fish lines, including alx:GFP, gata3:GFP, scl:GFP, dbx1b:GFP, and nkx2.2b:GFP. We have been investigating development and function of neurons that express these genes by the combination of anatomical and electrophysiological methods.

2) Analysis of spinal neuronal circuits by artificially altering activities of a specific class of neurons.
As an alternative approach, we have been investigating the function of a particular class of neurons by artificially altering their activities. Toward this end, we have made transgenic fish that express the tetanus-toxin gene (a blocker of synaptic transmission) under the promoter of a transcription factor (for example, alx). We have been investigating the behavioral consequences of these fish, and thereby trying to elucidate the function of the neurons that express a particular transcription factor.

SELECTED PUBLICATIONS

1. "V2a and V2b neurons are generated by the final divisions of pair-producing progenitors in the zebrafish spinal cord." Development 135, 3001-3005 (2008)
2. "alx, a zebrafish homolog of Chx10, marks ipsilateral descending excitatory interneurons that participate in the regulation of spinal locomotor circuits." J. Neuroscience 26, 5684-5697 (2006)
3. "Engrailed-1 expression marks a primitive class of inhibitory spinal interneuron." J. Neuroscience 24, 5827-5839 (2004)