Suzuki, S.C., Bleckert, A., Williams, P.R., Takechi, M., Kawamura, S., and Wong, R.O. (2013) Cone photoreceptor types in zebrafish are generated by symmetric terminal divisions of dedicated precursors. Proceedings of the National Academy of Sciences of the United States of America. 110(37):15109-14.
Proper functioning of sensory systems requires the generation of appropriate numbers and proportions of neuronal subtypes
that encode distinct information. Perception of color relies on signals from multiple cone photoreceptor types. In cone-dominated
retinas, each cone expresses a single opsin type with peak sensitivity to UV, long (L) (red), medium (M) (green), or short
(S) (blue) wavelengths. The modes of cell division generating distinct cone types are unknown. We report here a mechanism
whereby zebrafish cone photoreceptors of the same type are produced by symmetric division of dedicated precursors. Transgenic
fish in which the thyroid hormone receptor β2 (trβ2) promoter drives fluorescent protein expression before L-cone precursors themselves are produced permitted tracking of their
division in vivo. Every L cone in a local region resulted from the terminal division of an L-cone precursor, suggesting that
such divisions contribute significantly to L-cone production. Analysis of the fate of isolated pairs of cones and time-lapse
observations suggest that other cone types can also arise by symmetric terminal divisions. Such divisions of dedicated precursors
may help to rapidly attain the final numbers and proportions of cone types (L > M, UV > S) in zebrafish larvae. Loss- and
gain-of-function experiments show that L-opsin expression requires trβ2 activity before cone differentiation. Ectopic expression of trβ2 after cone differentiation produces cones with mixed opsins. Temporal differences in the onset of trβ2 expression could explain why some species have mixed, and others have pure, cone types.