Shen, D., Chu, J., Zhou, X., Lan, Z., Zhang, R., Wang, S., Tang, H., Wang, Y., Hu, C., Li, Z., Song, Y. (2026). Temporal neuronal differentiation programs safeguard neuronal diversity. Proc. Natl. Acad. Sci. U.S.A. 123(14): e2527895123.
FlyBase ID
FBrf0265020
Publication Type
Research paper
Abstract
Differentiation programs actively lock neurons into a terminally differentiated state. How differentiation programs operate in distinct neuronal lineages remains obscure. Here, we found that previously well-characterized Drosophila neuronal differentiation factors are specifically expressed in the central brain late-born neurons but not early-born neurons, indicating the existence of a distinct, early differentiation program. We next identified T cell factor (TCF) and Odd-paired (Opa)/Zic as part of the early differentiation program that is specifically expressed in the early-born neurons to prevent neuronal dedifferentiation, partly through restricting Chinmo expression. At the molecular level, TCF promotes neuronal differentiation through a Wnt-independent noncanonical mode, via forming a transcriptional complex with Opa. Together, our study unveils that distinct differentiation programs operate in fly central brain early-born versus late-born neurons. Such customized differentiation mechanism whereby temporal differentiation programs safeguard their corresponding temporal identity specification programs is likely to also operate in mammalian brain development.
