The role of Diencephalon/Mesencephalon Homeobox 1 (Dmbx1) in Zebrafish Visual System Development

Visual system development is highly conserved across all vertebrates. The retina receives visual inputs and transfers the sensory information to the brain for processing. In zebrafish, the largest synaptic target of the retinal projections is the optic tectum, which acts as a relay center that organizes visuomotor activities. My research has revealed that the transcriptional regulator Diencephalon/mesencephalon homeobox 1 (dmbx1), of which there are two paralogs represented in the zebrafish genome, plays a pivotal role in coordinating neurogenesis in these functionally integrated regions. During the course of my doctoral research, I have characterized the functions of dmbx1 paralogs in zebrafish retinal and tectal development and showed that they are required for sustaining growth in the retina and the optic tectum. Functional deficiency of the dmbx1 genes caused a severe cell cycle defect in progenitor cells, resulting in reduced tissue growth and delayed differentiation within those structures. Further analysis revealed that progenitor cells require dmbx1 to reduce the level of cyclinD1 expression, in order to promote cell cycle exit. In addition, I discovered that misexpression of both dmbx1 genes could duplicate wnt3a expression and lead to enhanced proliferation at the tectal midline. This suggested that the two transcription factors could regulate different cellular mechanisms with the presence of canonical Wnt signaling. Overall, this research demonstrates that dmbx1 is involved in the timing of retinal and tectal neurogenesis, and provides novel insight into the transcriptional regulation of visual system development in vertebrates.Ph