When few RGCs are around, radial division (shown) can be converted to cirumferential.

In mammals, cells that divide with their spindle axis parallel to the surface of the epithelial sheet produce symmetric daughters, whereas a spindle perpendicular to the sheet produces asymmetric progeny. Poggi et al. (page 991) report that environmental factors can affect spindle orientation in the zebrafish retina and thus alter cell fate.

Retinal ganglion cell (RGC) formation is dependent on Ath5. Using time-lapse microscopy, the team found that as cells began to express Ath5 they migrated toward the outer surface of the cup-shaped retina. Once there, the cells divided one time, with the plane of their spindle oriented along the radial axis of the retina (i.e., perpendicular to the sheet). One daughter cell migrated back toward the center of the retina and became an RGC, while the other remained near the outer surface and differentiated into a different cell type.

When GFP-marked, wild-type cells were transplanted to embryos lacking Ath5, the cell division pattern changed. As in wild-type retinas, the cells moved to the periphery upon Ath5 expression and usually divided once. However, instead of orienting their spindle along the radial axis, the spindle was often oriented along the circumferential axis, and both daughters became RGCs.

It was known previously that the presence of a large number of RGCs decreased the likelihood that more RGCs would be formed, but how that happened was not clear. Poggi et al. hypothesize that a factor secreted by the RGCs influences the orientation of the spindle, and therefore the lineage pattern of Ath5-expressing progenitors. Thus it appears that daughter cell fate depends both on lineage and environmental cues.A hint as to how spindle orientation can be altered may come from a recent paper ((igman et al. 2005. Neuron. 48:539–545). They found that RNAi knockdown of a mammalian homologue of Inscuteable, a key regulator of spindle orientation in flies, results in the misorientation of spindles in neuroepithelia of rat retinal explants. The spindle changes result in cell fate changes reminiscent of those reported by Poggi et al.