HALE, ME; KHEIRBEK, MA; PRINCE, VE; Univ. of Chicago; Univ. of Chicago; Univ. of Chicago: Hox gene misexpression generates functional neurons in zebrafish locomotor neural circuits.

Startle behaviors of fishes are initiated by neurons with cell bodies in the hindbrain and axons that extend along the length of the spinal cord. Such neurons include the paired Mauthner cells (M-cells) in rhombomere (r) 4 and their serial homologs. In recent experiments on the role of Hox genes in brain patterning, a second pair of M-cells has been induced in r2 through misexpression of Hoxb1b (McClintock et al. 2001 Development 128:2471-2484). As variation in Hox gene expression is a likely mechanism by which systems such as the M-cell and its homologs evolve, we examined the function of the r2 M-cell in startle behavior to investigate this process. We used calcium imaging to determine r4 and r2 M-cell activity. The r2 M-cell responds to the same stimulus intensity as the r4 M-cell indicating that the r2 M-cell is appropriately connected to sensory neurons. Experiments lesioning the r2 M-cell, r4 M-cell or both, show that, while removing the Mauthner cell from a normal wild type fish causes decreased startle performance, no such decrease occurs when the r4 M-cell is ablated if the r2 M-cell is present. The lesion data indicate that the r2 Mauthner cell has established the correct connections to downstream neurons to ensure an appropriate motor response. These experiments suggest that, when a cell duplication event or change in cell identity occurs, the new cell, at its formation, can be integrated into sensory and motor pathways and can function in a neural circuit. However, that the functions of the r4 and r2 M-cells are redundant suggests such cells may not immediately serve independent roles in motor control.