Tbx2b is essential for neuronal differentiation along the dorsal/ventral axis of the zebrafish retina

Abstract

The mechanisms by which retinal neurons are patterned along the dorsal/ventral axis remain largely unknown, yet this patterning is integral for the topographic mapping of visual space. With an interest in elucidating the mechanisms that regulate the development of this retinal axis, we have characterized a T-box family transcription factor, Tbx2b, during zebrafish retinogenesis. Tbx2b is expressed throughout all phases of retinal development with a striking asymmetry of distribution highest dorsally to lowest ventrally. To examine Tbx2b function during retinal development, two morpholino antisense oligonucleotides were created; one blocking the translational start site of Tbx2b and the other interfering with Tbx2b mRNA splicing. Injection of either of these morpholinos resulted in profound defects in the development of the dorsal retina. By using molecular markers for neuronal subtypes, the ventral retina contained all cell types, whereas in the dorsal retina, only retinal ganglion cells expressed markers of differentiation. The cells of the dorsal retina were postmitotic, however, as demonstrated by a lack of BrdUrd incorporation during the normal periods of retinal differentiation. Markers for dorsal and ventral retinal compartments were also expressed normally in Tbx2b morphants. Combined, these observations suggest that the cellular mechanisms regulating neuronal differentiation within the retina are asymmetric about the dorsal/ventral axis and that Tbx2b mediates this process within the dorsal retina.