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.
Shen et al. (Mon,) studied this question.