Mitotic Position and Morphology of Committed Precursor Cells in the Zebrafish Retina Adapt to Architectural Changes upon Tissue Maturation

Summary: The development of complex neuronal tissues like the vertebrate retina requires the tight orchestration of cell proliferation and differentiation. Although the complexity of transcription factors and signaling pathways involved in retinogenesis has been studied extensively, the influence of tissue maturation itself has not yet been systematically explored. Here, we present a quantitative analysis of mitotic events during zebrafish retinogenesis that reveals three types of committed neuronal precursors in addition to the previously known apical progenitors. The identified precursor types present at distinct developmental stages and exhibit different mitotic location (apical versus nonapical), cleavage plane orientation, and morphology. Interestingly, the emergence of nonapically dividing committed bipolar cell precursors can be linked to an increase in apical crowding caused by the developing photoreceptor cell layer. Furthermore, genetic interference with neuronal subset specification induces ectopic divisions of committed precursors, underlining the finding that progressing morphogenesis can effect precursor division position. : Vertebrate retinogenesis is a complex phenomenon that requires the precise orchestration of cell proliferation and differentiation. Weber et al. extend what is known about retinogenesis by showing that, at late stages of retinal developmental, the majority of mitotic figures originate from diverse committed precursors featuring different morphology and dividing at various locations. Furthermore, tissue maturation and arising tissue obstacles, such as the emerging photoreceptor cell layer, are shown to play a role in repositioning mitotic cell precursors