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Combinatorial temporal patterning in progenitors expands neural diversity

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Abstract

Human outer subventricular zone (OSVZ) neural progenitors and Drosophila type II neuroblasts both generate intermediate neural progenitors (INPs) that populate the adult cerebral cortex or central complex, respectively. It is unknown whether INPs simply expand or also diversify neural cell types. Here we show that Drosophila INPs sequentially generate distinct neural subtypes, that INPs sequentially express Dichaete, Grainy head and Eyeless transcription factors, and that these transcription factors are required for the production of distinct neural subtypes. Moreover, parental type II neuroblasts also sequentially express transcription factors and generate different neuronal/glial progeny over time, providing a second temporal identity axis. We conclude that neuroblast and INP temporal patterning axes act together to generate increased neural diversity within the adult central complex; OSVZ progenitors may use similar mechanisms to increase neural diversity in the human brain.

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Figure 1: INPs sequentially express candidate temporal identity factors.
Figure 2: Cross-regulation between INP temporal transcription factors.
Figure 3: INPs sequentially generate distinct temporal identities.
Figure 4: Eyeless is a temporal identity factor for late born INP progeny.
Figure 5: Eyeless is required for adult brain central complex morphology and behaviour.
Figure 6: INP temporal patterning acts combinatorially with neuroblast temporal patterning to increase neural diversity.

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Change history

  • 26 June 2013

    A minor change was made to the shading in Fig. 6c.

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Acknowledgements

We thank L. Manning and K. Hirono for larval brain stains and imaging; S.-L. Lai, J. Eisen, T. Herman and B. Bowerman for comments on the manuscript; T. Carney and M. Miller for discussions; and the fly community for reagents. This work was supported by National Institutes of Health (NIH) grants T32HD216345 and T32GM007413 (to O.A.B.), NIH R01HD27056 (to C.Q.D.) and the Howard Hughes Medical Institute (to C.Q.D.).

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O.A.B. performed the experiments; O.A.B. and C.Q.D. conceived of the project and wrote the manuscript.

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Correspondence to Chris Q. Doe.

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The authors declare no competing financial interests.

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Supplementary Information

This file contains Supplementary Figures 1-12 and Supplementary Tables 1-5. (PDF 5089 kb)

Ey-RNAi adult flies are defective in negative geotaxis

Ey-RNAi flies (right vial) have relatively normal locomotion, but have a significant deficit in negative geotaxis compared to control flies (left vial). Negative geotaxis was assessed by the number of flies that climb above the vertical distance of 8 cm (marked on vials) by 10 seconds. (MOV 15543 kb)

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Bayraktar, O., Doe, C. Combinatorial temporal patterning in progenitors expands neural diversity. Nature 498, 449–455 (2013). https://doi.org/10.1038/nature12266

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