Abstract

During CNS development there is prominent expansion of the anterior region, the brain. In Drosophila, anterior CNS expansion emerges from three rostral features: 1) increased progenitor cell generation, 2) extended progenitor cell proliferation, 3) more proliferative daughters. We find that tailless (mouse Nr2E1/Tlx), otp/Rx/hbn (Otp/Arx/Rax) and Doc1/2/3 (Tbx2/3/6) are important for brain progenitor generation. These genes, and earmuff (FezF1/2), are also important for subsequent progenitor and/or daughter cell proliferation in the brain. Brain TF co-misexpression can drive brain-profile proliferation in the nerve cord, and can reprogram developing wing discs into brain neural progenitors. Brain TF expression is promoted by the PRC2 complex, acting to keep the brain free of anti-proliferative and repressive action of Hox homeotic genes. Hence, anterior expansion of the Drosophila CNS is mediated by brain TF driven 'super-generation' of progenitors, as well as 'hyper-proliferation' of progenitor and daughter cells, promoted by PRC2-mediated repression of Hox activity.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jesús Rodriguez Curt

    Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  2. Behzad Yaghmaeian Salmani

    Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Stefan Thor

    Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden
    For correspondence
    stefan.thor@liu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5095-541X

Funding

Knut och Alice Wallenbergs Stiftelse (KAW2011.0165)

  • Stefan Thor

Vetenskapsrådet (621-2013-5258)

  • Stefan Thor

Cancerfonden (140780; 150663)

  • Stefan Thor

Knut och Alice Wallenbergs Stiftelse (KAW2012.0101)

  • Stefan Thor

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Publication history

  1. Received: January 17, 2019
  2. Accepted: July 3, 2019
  3. Accepted Manuscript published: July 4, 2019 (version 1)
  4. Version of Record published: July 16, 2019 (version 2)

Copyright

© 2019, Curt et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,921
    Page views
  • 296
    Downloads
  • 13
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Jesús Rodriguez Curt
  2. Behzad Yaghmaeian Salmani
  3. Stefan Thor
(2019)
Anterior CNS expansion driven by brain transcription factors
eLife 8:e45274.
https://doi.org/10.7554/eLife.45274

Further reading

    1. Stem Cells and Regenerative Medicine
    2. Developmental Biology
    Jaydeep Sidhaye, Philipp Trepte ... Jürgen A Knoblich
    Research Article

    During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the posttranscriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using human telencephalic brain organoids grown using a dual reporter cell line to isolate neural progenitors and neurons and performed cell class and developmental stage-specific transcriptome and proteome analysis. Integrating the two datasets revealed modules of gene expression during human corticogenesis. Investigation of one such module uncovered mTOR-mediated regulation of translation of the 5’TOP element-enriched translation machinery in early progenitor cells. We show that in early progenitors partial inhibition of the translation of ribosomal genes prevents precocious translation of differentiation markers. Overall, our multiomics approach proposes novel posttranscriptional regulatory mechanisms crucial for the fidelity of cortical development.

    1. Developmental Biology
    2. Neuroscience
    Kenneth Kin Lam Wong, Tongchao Li ... Liqun Luo
    Research Article

    How does wiring specificity of neural maps emerge during development? Formation of the adult Drosophila olfactory glomerular map begins with patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon- and adaptive optical lattice light-sheet microscope-based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps.