During retinal development in vertebrates, six types of neuron and one type of glial cell are generated in a defined temporal sequence. Two recent reports in Neuron identify transcription factors that are required for the development of three of the neuronal cell types.

In the first study, Bramblett et al. showed that the basic helix–loop–helix factor Bhlhb4 is required for the maturation — but not the initial specification — of rod bipolar (RB) cells. The RB cells reside in the inner nuclear layer (INL) of the retina, and they relay information from rod photoreceptors to amacrine and retinal ganglion cells. In a Bhlhb4−/− mouse, RB cells were born normally, but they failed to survive. The most extensive RB-cell loss was observed around postnatal day 8, which is when Bhlhb4 expression normally peaks.

The winged helix/forkhead transcription factor Foxn4 is expressed in progenitor cells that give rise to two other types of neuron in the INL: amacrine cells and horizontal cells. In the second study, Li et al. showed that a Foxn4 gene knockout in mice caused a profound reduction in the number of amacrine cells, and a total absence of horizontal cells. Foxn4 seems to control amacrine cell development by regulating the expression of the bHLH factors Math3 and NeuroD1, and is both necessary and sufficient to promote an amacrine cell fate. With regard to the horizontal cells, Foxn4 seems to have a permissive rather than an instructive role: it can make progenitor cells competent to generate horizontal cells, but cannot promote a horizontal-cell fate on its own.

Until recently, the molecular basis of retinal neurogenesis was poorly understood, but findings such as these will undoubtedly enhance our knowledge of the mechanisms that generate and maintain the diverse range of cells that coordinate retinal function.