Wnt Signaling Regulates Ipsilateral Pathfinding in the Zebrafish Forebrain through slit3.

The nervous system relies upon correct interconnections to exert its normal function. During vertebrate embryonic development, highly stereotyped scaffolds of axon tracts are formed early in the brain to set the foundation for the neuronal interconnections. During zebrafish early development, anterior dorsal telencephalic (ADt) neurons extend axons along the ipsilateral supraoptic tract (SOT) and the contralateral anterior commissure (AC). Our previous study shows axonal outgrowths along the AC/SOT tracts are coordinated by the guidance molecules Dcc-Netrin and Robo2-Slit, but it is not known how the expressions of these guidance molecules are regulated in the forebrain tissues. Here we show ectopic activation of Wnt signaling abolishes the ipsilateral SOT originating from the ADt neurons. Further mechanistic studies show ectopic activation of Wnt signaling significantly reduces Slits' expression, whilst mis-expression of Slit3 rescues SOT outgrowth. Together, our findings indicate Wnt signaling controls the ipsilateral axonal outgrowth through the regulation of slits' expression in the zebrafish forebrain.