Abstract
Nervous systems are incredibly diverse, with myriad neuronal subtypes that can be defined by gene expression. Some features appear binary, with genes that are either on or off, whereas others are graded, with a range of gene expression. How binary and graded cell fate characteristics are controlled within individual cells to pattern tissues is poorly understood. To address this question, we quantitatively analyzed cone subtype specification in the mouse retina. Cone cells in the mouse retina express two photopigments; UV light-detecting S-opsin and green light-detecting M-opsin. We developed an automated image analysis approach to identify individual cones and assess their opsin expression. Cones make a binary decision between S-opsin only and co-expression competent fates. Co-expression competent cells express graded levels of both S- and M-opsins, depending on their position in the dorsal to ventral axis of the retina. M- and S-opsin expression levels display differential, inverse patterns of expression. Whereas M-opsin is highly expressed in the dorsal retina and slowly decreases in the central and ventral retina, S-opsin is lowly expressed in the dorsal retina and increases rapidly from the dorsal to central retina. Previous studies found that thyroid hormone signaling plays a critical role in controlling cone opsin expression. We developed a quantitative model based on thyroid hormone pathway activity that describes the patterning of the binary and graded features of cone fate in the mouse retina. Our studies provide a paradigm describing how differential responses to regulatory inputs generate complex patterns of binary and graded cell fates.