Abstract
Neural progenitors undergo temporal patterning to generate diverse neurons in a chronological order. This process is well-studied in the developing Drosophila brain and conserved in mammals. During larval stages, intermediate neural progenitors (INPs) serially express Dichaete (D), grainyhead (Grh) and eyeless (Ey/Pax6), but how the transitions are regulated is not precisely understood. Here, we developed a method to isolate transcriptomes of INPs in their distinct temporal states to identify a complete set of temporal patterning factors. Our analysis identifies odd-paired (opa), as a key regulator of temporal patterning. Temporal patterning is initiated when the SWI/SNF complex component Osa induces D and its repressor Opa at the same time but with distinct kinetics. Then, high Opa levels repress D to allow Grh transcription and progress to the next temporal state. We propose that Osa and its target genes opa and D form an incoherent feedforward loop (FFL) and a new mechanism allowing the successive expression of temporal identities.
Highlights
During brain development, neural stem cells (NSCs) generate large numbers of highly diverse neuronal and glial cells in chronological order (Cepko, Austin, Yang, Alexiades, & Ezzeddine, 1996;; Gao et al, 2014;; Greig, Woodworth, Galazo, Padmanabhan, & Macklis, 2013;; Holguera & Desplan, 2018)
As Opa is a direct target of Osa (Eroglu et al, 2014) we investigated the potential role of Opa in regulating intermediate neural progenitors (INPs) temporal patterning. 155 Odd-paired is required for the progression of INP temporal patterning Opa is a transcription factor containing five zinc finger domains and is essential for para-segmental subdivision of Drosophila embryos (Benedyk, Mullen, & DiNardo, 1994;; Mizugishi, Aruga, Nakata, & Mikoshiba, 2001)
We identified odd-paired 289, a transcription factor that is required for INP temporal patterning
Summary
Neural stem cells (NSCs) generate large numbers of highly diverse neuronal and glial cells in chronological order (Cepko, Austin, Yang, Alexiades, & Ezzeddine, 1996;; Gao et al, 2014;; Greig, Woodworth, Galazo, Padmanabhan, & Macklis, 2013;; Holguera & Desplan, 2018). Wang et al, 2016), Ikaros (the ortholog of the Drosophila Hunchback), in contrast, is an intrinsic factor specifying early-born neuronal fates (Mattar, Ericson, Blackshaw, & Cayouette, 2015b). Like Ikaros, intrinsic temporal identity factors in vertebrates are often homologous to factors described in Drosophila (Naka, Nakamura, Shimazaki, & Okano, 2008;; Ren et al, 2017;; Syed, Mark, & Doe, 2017). How these factors are involved in neuronal fate specification and how they are regulated remain unknown
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