Hair follicle dermal condensation forms via Fgf20 primed cell cycle exit, cell motility, and aggregation

Abstract

Mesenchymal condensation is a critical step in organogenesis, yet the underlying molecular and cellular mechanisms remain poorly understood. The hair follicle dermal condensate is the precursor to the permanent mesenchymal unit of the hair follicle, the dermal papilla, which regulates hair cycling throughout life and bears hair inductive potential. Dermal condensate morphogenesis depends on epithelial Fibroblast Growth Factor 20 (Fgf20). Here, we combine mouse models with 3D and 4D microscopy to demonstrate that dermal condensates form de novo and via directional migration. We identify cell cycle exit and cell shape changes as early hallmarks of dermal condensate morphogenesis and find that Fgf20 primes these cellular behaviors and enhances cell motility and condensation. RNAseq profiling of immediate Fgf20 targets revealed induction of a subset of dermal condensate marker genes. Collectively, these data indicate that dermal condensation occurs via directed cell movement and that Fgf20 orchestrates the early cellular and molecular events.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE110459. All data analyzed for this study are included in the manuscript and supporting files. Source data files have been provided where appropriate.

The following data sets were generated

Article and author information

Author details

  1. Leah C Biggs

    Developmental Biology Program, University of Helsinki, Helsinki, Finland
    For correspondence
    leah.biggs@helsinki.fi
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4990-8664
  2. Otto J.M. Mäkelä

    Developmental Biology Program, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6852-9814
  3. Satu-Marja Myllymäki

    Developmental Biology Program, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  4. Rishi Das Roy

    Developmental Biology Program, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  5. Katja Närhi

    Developmental Biology Program, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  6. Johanna Pispa

    Developmental Biology Program, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  7. Tuija Mustonen

    Developmental Biology Program, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2429-5064
  8. Marja L Mikkola

    Developmental Biology Program, University of Helsinki, Helsinki, Finland
    For correspondence
    marja.mikkola@helsinki.fi
    Competing interests
    The authors declare that no competing interests exist.

Funding

Sigrid Juséliuksen Säätiö

  • Marja L Mikkola

Jane and Aatos Erkko Foundation

  • Marja L Mikkola

Doctoral Program in Integrative Life Science of the University of Helsinki

  • Otto J.M. Mäkelä

Academy of Finland (268798)

  • Marja L Mikkola

Academy of Finland (307421)

  • Marja L Mikkola

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

Ethics

Animal experimentation: All mouse studies were approved and carried out in accordance with the guidelines of the Finnish national animal experimentation board under licenses KEK16-021 and ESAV/2363/04.10.07/2017.

Reviewing Editor

  1. Valerie Horsley, Yale University, United States

Publication history

  1. Received: March 7, 2018
  2. Accepted: July 30, 2018
  3. Accepted Manuscript published: July 31, 2018 (version 1)
  4. Version of Record published: August 23, 2018 (version 2)

Copyright

© 2018, Biggs 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

  • 3,210
    Page views
  • 450
    Downloads
  • 23
    Citations

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

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. Leah C Biggs
  2. Otto J.M. Mäkelä
  3. Satu-Marja Myllymäki
  4. Rishi Das Roy
  5. Katja Närhi
  6. Johanna Pispa
  7. Tuija Mustonen
  8. Marja L Mikkola
(2018)
Hair follicle dermal condensation forms via Fgf20 primed cell cycle exit, cell motility, and aggregation
eLife 7:e36468.
https://doi.org/10.7554/eLife.36468

Further reading

    1. Cell Biology
    Desiree Schatton et al.
    Research Article

    Proliferating cells undergo metabolic changes in synchrony with cell cycle progression and cell division. Mitochondria provide fuel, metabolites, and ATP during different phases of the cell cycle, however it is not completely understood how mitochondrial function and the cell cycle are coordinated. CLUH is a post-transcriptional regulator of mRNAs encoding mitochondrial proteins involved in oxidative phosphorylation and several metabolic pathways. Here, we show a role of CLUH in regulating the expression of astrin, which is involved in metaphase to anaphase progression, centrosome integrity, and mTORC1 inhibition. We find that CLUH binds both the SPAG5 mRNA and its product astrin, and controls the synthesis and the stability of the full-length astrin-1 isoform. We show that CLUH interacts with astrin-1 specifically during interphase. Astrin-depleted cells show mTORC1 hyperactivation and enhanced anabolism. On the other hand, cells lacking CLUH show decreased astrin levels and increased mTORC1 signaling, but cannot sustain anaplerotic and anabolic pathways. In absence of CLUH, cells fail to grow during G1, and progress faster through the cell cycle, indicating dysregulated matching of growth, metabolism and cell cycling. Our data reveal a role of CLUH in coupling growth signaling pathways and mitochondrial metabolism with cell cycle progression.

    1. Cell Biology
    Dillon Jevon et al.
    Research Article

    A developing understanding suggests that spatial compartmentalisation in pancreatic β cells is critical in controlling insulin secretion. To investigate the mechanisms, we have developed live-cell sub-cellular imaging methods using the mouse organotypic pancreatic slice. We demonstrate that the organotypic pancreatic slice, when compared with isolated islets, preserves intact β cell structure, and enhances glucose dependent Ca2+ responses and insulin secretion. Using the slice technique, we have discovered the essential role of local activation of integrins and the downstream component, focal adhesion kinase, in regulating β cells. Integrins and focal adhesion kinase are exclusively activated at the β cell capillary interface and using in situ and in vitro models we show their activation both positions presynaptic scaffold proteins, like ELKS and liprin, and regulates glucose dependent Ca2+ responses and insulin secretion. We conclude that focal adhesion kinase orchestrates the final steps of glucose dependent insulin secretion within the restricted domain where β cells contact the islet capillaries.