Intermediate neural progenitors (INPs) need to avoid both dedifferentiation and differentiation during neurogenesis, but the underlying mechanisms are not well understood. In Drosophila, the Ets protein Pointed P1 (PntP1) is required to generate INPs from type II neuroblasts. Here, we investigated how PntP1 promotes INP generation. By generating pntP1-specific mutants and using RNAi knockdown, we show that the loss of PntP1 leads to both an increase in type II neuroblast number and the elimination of INPs. The elimination of INPs results from the premature differentiation of INPs due to ectopic Prospero expression in newly generated immature INPs (imINPs), whereas the increase in type II neuroblasts results from the dedifferentiation of imINPs due to loss of Earmuff at later stages of imINP development. Furthermore, reducing Buttonhead enhances the loss of INPs in pntP1 mutants, suggesting that PntP1 and Buttonhead act cooperatively to prevent premature INP differentiation. Our results demonstrate that PntP1 prevents both the premature differentiation and the dedifferentiation of INPs by regulating the expression of distinct target genes at different stages of imINP development.
The authors declare no competing or financial interests.
S.Z. and Y.X. designed the project and approaches, interpreted data and wrote the paper. Y.X., X.L., Y.H. and X.D. conducted experiments and analyzed the data. K.O., A.U. and L.C. provided technical support. Y.P. designed the strategy for generating pntP1 mutants. Y.H., X.D., K.O., Y.P. and L.C. contributed to manuscript editing.
This work was supported by a March of Dimes Foundation Basil O'Connor Starter Scholar Research Award [#5-FY14-59 to S.Z.]; and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health [R01NS085232 to S.Z.]. Deposited in PMC for release after 12 months.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.137281.supplemental
- Received March 7, 2016.
- Accepted July 27, 2016.