Background:The highly ordered vertebrate retina is composed of seven cell types derived from a common pool of retinal progenitor cells (RPCs), and is a good model for the studies of cell differentiation and interaction during neural development. Notch signaling plays a pivotal role in retinogenesis in mammals, but the full scope of the functions of Notch pathway, and the underlying molecular mechanisms, remain unclear.
Results:In this study, we conditionally knocked outRBP-J, the critical transcription factor downstream to all four Notch receptors, in RPCs of mouse retina atdifferent developmental stages. Disruption of RBP-J at early retinogenesis resulted in accelerated RPCs differentiation, but only photoreceptors and ganglion cells were overrepresented, with other neuronal populations diminished. Similarly, deletion ofRBP-Jat early postnatal days also led to overproduction of photoreceptors, suggesting that RBP-J governed RPCs specification anddifferentiation through retinogenesis. In all the RBP-J deletion models, the retinal laminar structures were distorted by the formation of numerous rosette-like structures, reminiscent of β-catenin deficient retina. Indeed, we found that these rosettes aligned with gaps in β-catenin expression at the apical surface of the retina. By in vivo electroporation-mediated transfection, we demonstrated that lamination defects in RBP-J deficient retinae were rescued by overexpressing β-catenin.
Conclusions:Our data indicate that RBP-J-mediated canonical Notch signaling governs retinal cell specification and differentiation, and maintainsretinal lamination through the expression ofβ- catenin