|ZFIN ID: ZDB-PUB-070813-10|
Six3 represses nodal activity to establish early brain asymmetry in zebrafish
Inbal, A., Kim, S.H., Shin, J., and Solnica-Krezel, L.
|Source:||Neuron 55(3): 407-415 (Journal)|
|Registered Authors:||Inbal, Adi, Kim, Seok-Hyung, Shin, Jimann, Solnica-Krezel, Lilianna|
|PubMed:||17678854 Full text @ Neuron|
Inbal, A., Kim, S.H., Shin, J., and Solnica-Krezel, L. (2007) Six3 represses nodal activity to establish early brain asymmetry in zebrafish. Neuron. 55(3):407-415.
ABSTRACTThe vertebrate brain is anatomically and functionally asymmetric; however, the molecular mechanisms that establish left-right brain patterning are largely unknown. In zebrafish, asymmetric left-sided Nodal signaling within the developing dorsal diencephalon is required for determining the direction of epithalamic asymmetries. Here, we show that Six3, a transcription factor essential for forebrain formation and associated with holoprosencephaly in humans, regulates diencephalic Nodal activity during initial establishment of brain asymmetry. Reduction of Six3 function causes brain-specific deregulation of Nodal pathway activity, resulting in epithalamic laterality defects. Based on misexpression and genetic epistasis experiments, we propose that Six3 acts in the neuroectoderm to establish a prepattern of bilateral repression of Nodal activity. Subsequently, Nodal signaling from the left lateral plate mesoderm alleviates this repression ipsilaterally. Our data reveal a Six3-dependent mechanism for establishment of correct brain laterality and provide an entry point to understanding the genetic regulation of Nodal signaling in the brain.