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Regulation of neuroblast competence in Drosophila

Abstract

Individual neural progenitors generate different cell types in a reproducible order in the retina1,2,3, cerebral cortex4,5,6 and probably in the spinal cord7. It is unknown how neural progenitors change over time to generate different cell types. It has been proposed that progenitors undergo progressive restriction8 or transit through distinct competence states9,10; however, the underlying molecular mechanisms remain unclear. Here we investigate neural progenitor competence and temporal identity using an in vivo genetic system—Drosophila neuroblasts—where the Hunchback transcription factor is necessary and sufficient to specify early-born cell types11. We show that neuroblasts gradually lose competence to generate early-born fates in response to Hunchback, similar to progressive restriction models8, and that competence to acquire early-born fates is present in mitotic precursors but is lost in post-mitotic neurons. These results match those observed in vertebrate systems, and establish Drosophila neuroblasts as a model system for the molecular genetic analysis of neural progenitor competence and plasticity.

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Figure 1: The early lineage of NB7-1.
Figure 2: NB7-1 shows plasticity in response to Hunchback.
Figure 3: Mitotic progenitors but not post-mitotic neurons show competence to respond to Hunchback.
Figure 4: Summary of NB, GMC and neuronal competence to respond to Hb.

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References

  1. Turner, D. L. & Cepko, C. L. A common progenitor for neurons and glia persists in rat retina late in development. Nature 328, 131–136 (1987)

    Article  ADS  CAS  Google Scholar 

  2. Perron, M., Kanekar, S., Vetter, M. L. & Harris, W. A. The genetic sequence of retinal development in the ciliary margin of the Xenopus eye. Dev. Biol. 199, 185–200 (1998)

    Article  CAS  Google Scholar 

  3. Cepko, C. L., Austin, C. P., Yang, X., Alexiades, M. & Ezzeddine, D. Cell fate determination in the vertebrate retina. Proc. Natl Acad. Sci. USA 93, 589–595 (1996)

    Article  ADS  CAS  Google Scholar 

  4. McConnell, S. K. The determination of neuronal fate in the cerebral cortex. Trends Neurosci. 12, 342–349 (1989)

    Article  CAS  Google Scholar 

  5. Angevine, J. B. Jr & Sidman, R. L. Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse. Nature 192, 766–768 (1961)

    Article  ADS  Google Scholar 

  6. Qian, X. et al. Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells. Neuron 28, 69–80 (2000)

    Article  CAS  Google Scholar 

  7. Zhou, Q. & Anderson, D. J. The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell 109, 61–73 (2002)

    Article  CAS  Google Scholar 

  8. Desai, A. R. & McConnell, S. K. Progressive restriction in fate potential by neural progenitors during cerebral cortical development. Development 127, 2863–2872 (2000)

    CAS  PubMed  Google Scholar 

  9. Livesey, F. J. & Cepko, C. L. Vertebrate neural cell-fate determination: lessons from the retina. Nature Rev. Neurosci. 2, 109–118 (2001)

    Article  CAS  Google Scholar 

  10. Rapaport, D. H., Patheal, S. L. & Harris, W. A. Cellular competence plays a role in photoreceptor differentiation in the developing Xenopus retina. J. Neurobiol. 49, 129–141 (2001)

    Article  CAS  Google Scholar 

  11. Isshiki, T., Pearson, B., Holbrook, S. & Doe, C. Q. Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny. Cell 106, 511–521 (2001)

    Article  CAS  Google Scholar 

  12. Kambadur, R. et al. Regulation of POU genes by castor and hunchback establishes layered compartments in the Drosophila CNS. Genes Dev. 12, 246–260 (1998)

    Article  CAS  Google Scholar 

  13. Bossing, T., Udolph, G., Doe, C. Q. & Technau, G. M. The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm. Dev. Biol. 179, 41–64 (1996)

    Article  CAS  Google Scholar 

  14. Schmid, A., Chiba, A. & Doe, C. Q. Clonal analysis of Drosophila embryonic neuroblasts: neural cell types, axon projections and muscle targets. Development 126, 4653–4689 (1999)

    CAS  PubMed  Google Scholar 

  15. Landgraf, M., Bossing, T., Technau, G. M. & Bate, M. The origin, location, and projections of the embryonic abdominal motorneurons of Drosophila. J. Neurosci. 17, 9642–9655 (1997)

    Article  CAS  Google Scholar 

  16. Skeath, J. B. & Doe, C. Q. Sanpodo and Notch act in opposition to Numb to distinguish sibling neuron fates in the Drosophila CNS. Development 125, 1857–1865 (1998)

    CAS  PubMed  Google Scholar 

  17. Buenzow, D. E. & Holmgren, R. Expression of the Drosophila gooseberry locus defines a subset of neuroblast lineages in the central nervous system. Dev. Biol. 170, 338–349 (1995)

    Article  CAS  Google Scholar 

  18. Struhl, G., Johnston, P. & Lawrence, P. A. Control of the Drosophila body pattern by the hunchback morphogen gradient. Cell 69, 237–249 (1992)

    Article  CAS  Google Scholar 

  19. Zhang, C. C. & Bienz, M. Segmental determination in Drosophila conferred by hunchback (hb), a repressor of the homeotic gene Ultrabithorax (Ubx). Proc. Natl Acad. Sci. USA 89, 7511–7515 (1992)

    Article  ADS  CAS  Google Scholar 

  20. Sabbattini, P. et al. Binding of Ikaros to the lambda5 promoter silences transcription through a mechanism that does not require heterochromatin formation. EMBO J. 20, 2812–2822 (2001)

    Article  CAS  Google Scholar 

  21. Kehle, J. et al. dMi-2, a hunchback-interacting protein that functions in polycomb repression. Science 282, 1897–1900 (1998)

    Article  ADS  CAS  Google Scholar 

  22. Kim, J. et al. Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity 10, 345–355 (1999)

    Article  CAS  Google Scholar 

  23. Yang, X., Bahri, S., Klein, T. & Chia, W. Klumpfuss, a putative Drosophila zinc finger transcription factor, acts to differentiate between the identities of two secondary precursor cells within one neuroblast lineage. Genes Dev. 11, 1396–1408 (1997)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank J. Posakony, M. Fujioka and J. Jaynes for fly stocks; W. Odenwald and M. Lundell for antibodies; and R. Grosskortenhaus, M. Freeman, M. Rolls, T. Isshiki, M. Westerfield, T. Brody and W. Odenwald for comments. This work was funded by NIH and HHMI, where C.Q.D. is an Investigator.

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Correspondence to Chris Q. Doe.

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Supplementary information

41586_2003_BFnature01910_MOESM1_ESM.zip

Supplementary Movies: This ZIP files conatins two movies in MP4 format. Movie 1 (pearson_movie_s1.mp4): Birth-order and sibling relationships of the U motoneurons. Movie 2 (pearson_movie_s2.mp4): Re-expression of Hunchback in an older neuroblast generates ectopic U1 motoneurons with correct axon projections to the dorsal muscle field. (ZIP 1461 kb)

Supplementary Movie Legends (DOC 21 kb)

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Pearson, B., Doe, C. Regulation of neuroblast competence in Drosophila. Nature 425, 624–628 (2003). https://doi.org/10.1038/nature01910

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