NEUROD6 EXPRESSION DEFINES NOVEL RETINAL AMACRINE CELL SUBTYPES AND REGULATES THEIR FATE

Most regions of the central nervous system contain numerous subtypes of inhibitory interneurons that play specialized roles in circuit function. In mammalian retina, the ~30 subtypes of inhibitory interneurons called amacrine cells (ACs) are generally divided into two groups: wide/medium-field GABAergic and narrow-field glycinergic, which mediate lateral and vertical interactions, respectively, within the inner plexiform layer. We used expression profiling and mouse transgenic lines to identify and characterize two closely-related narrow-field AC subtypes. Both arise postnatally and one, surprisingly, is neither glycinergic nor GABAergic (nGnG). Two transcription factors selectively expressed by these subtypes, Neurod6 and Satb2, regulate a postmitotic cell fate choice between them. Satb2 induces Neurod6, which persists in nGnG ACs and promotes their fate, but is down-regulated in the related glycinergic AC subtype. Our results support the view that cell fate decisions made in progenitors and their progeny act together to diversify ACs.