1. Cell Biology
  2. Developmental Biology
Download icon

Drosophila Hedgehog can act as a morphogen in the absence of regulated Ci processing

  1. Jamie C Little
  2. Elisa Garcia-Garcia
  3. Amanda Sul
  4. Daniel Kalderon  Is a corresponding author
  1. Columbia University, United States
Research Article
  • Cited 3
  • Views 1,113
  • Annotations
Cite this article as: eLife 2020;9:e61083 doi: 10.7554/eLife.61083


Extracellular Hedgehog (Hh) proteins induce transcriptional changes in target cells by inhibiting the proteolytic processing of full-length Drosophila Ci or mammalian Gli proteins to nuclear transcriptional repressors and by activating the full-length Ci or Gli proteins. We used Ci variants expressed at physiological levels to investigate the contributions of these mechanisms to dose-dependent Hh signaling in Drosophila wing imaginal discs. Ci variants that cannot be processed supported a normal pattern of graded target gene activation and the development of adults with normal wing morphology, when supplemented by constitutive Ci repressor, showing that Hh can signal normally in the absence of regulated processing. The processing-resistant Ci variants were also significantly activated in the absence of Hh by elimination of Cos2, likely acting through binding the CORD domain of Ci, or PKA, revealing separate inhibitory roles of these two components in addition to their well-established roles in promoting Ci processing.

Data availability

All data reported in this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jamie C Little

    Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Elisa Garcia-Garcia

    Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Amanda Sul

    Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Kalderon

    Biological Sciences, Columbia University, New York, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2149-0673


National Institutes of Health (RO1 GM041815)

  • Daniel Kalderon

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

Reviewing Editor

  1. Claude Desplan, New York University, United States

Publication history

  1. Received: July 15, 2020
  2. Accepted: October 20, 2020
  3. Accepted Manuscript published: October 21, 2020 (version 1)
  4. Version of Record published: November 20, 2020 (version 2)


© 2020, Little 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.


  • 1,113
    Page views
  • 180
  • 3

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)

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

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

Further reading

    1. Cell Biology
    2. Plant Biology
    Julien Gronnier et al.
    Research Article Updated

    Spatial partitioning is a propensity of biological systems orchestrating cell activities in space and time. The dynamic regulation of plasma membrane nano-environments has recently emerged as a key fundamental aspect of plant signaling, but the molecular components governing it are still mostly unclear. The receptor kinase FERONIA (FER) controls ligand-induced complex formation of the immune receptor kinase FLAGELLIN SENSING 2 (FLS2) with its co-receptor BRASSINOSTEROID-INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1), and perception of the endogenous peptide hormone RAPID ALKALANIZATION FACTOR 23 (RALF23) by FER inhibits immunity. Here, we show that FER regulates the plasma membrane nanoscale organization of FLS2 and BAK1. Our study demonstrates that akin to FER, leucine-rich repeat (LRR) extensin proteins (LRXs) contribute to RALF23 responsiveness and regulate BAK1 nanoscale organization and immune signaling. Furthermore, RALF23 perception leads to rapid modification of FLS2 and BAK1 nanoscale organization, and its inhibitory activity on immune signaling relies on FER kinase activity. Our results suggest that perception of RALF peptides by FER and LRXs actively modulates plasma membrane nanoscale organization to regulate cell surface signaling by other ligand-binding receptor kinases.

    1. Cell Biology
    Paul M Wassarman, Eveline S Litscher
    Review Article

    Fertility in female mammals, including mice and humans, is dependent on the presence of a zona pellucida (ZP) around growing oocytes and unfertilized eggs. A ZP is required to stabilize contacts between oocyte microvilli and follicle cell projections that traverse the ZP to form gap junctions that support the health of growing oocytes and developing follicles. In the absence of a ZP, due to inactivation or mutation of genes encoding ZP proteins, there is a loss of contacts between growing oocytes and neighboring follicle cells and a concomitant reduction in the production of ovulated eggs that results in female infertility.