Thyroid hormone regulates distinct paths to maturation in pigment cell lineages

  1. Lauren M Saunders
  2. Abhishek K Mishra
  3. Andrew J Aman
  4. Victor M Lewis
  5. Matthew B Toomey
  6. Jonathan S Packer
  7. Xiaojie Qiu
  8. Jose L McFaline-Figueroa
  9. Joseph C Corbo
  10. Cole Trapnell  Is a corresponding author
  11. David M Parichy  Is a corresponding author
  1. University of Washington, United States
  2. University of Virginia, United States
  3. Washington University School of Medicine, United States

Abstract

Thyroid hormone (TH) regulates diverse developmental events and can drive disparate cellular outcomes. In zebrafish, TH has opposite effects on neural crest derived pigment cells of the adult stripe pattern, limiting melanophore population expansion, yet increasing yellow/orange xanthophore numbers. To learn how TH elicits seemingly opposite responses in cells having a common embryological origin, we analyzed individual transcriptomes from thousands of neural crest derived cells, reconstructed developmental trajectories, identified pigment cell-lineage specific responses to TH, and assessed roles for TH receptors. We show that TH promotes maturation of both cell types but in distinct ways. In melanophores, TH drives terminal differentiation, limiting final cell numbers. In xanthophores, TH promotes accumulation of orange carotenoids, making the cells visible. TH receptors act primarily to repress these programs when TH is limiting. Our findings show how a single endocrine factor integrates very different cellular activities during the generation of adult form.

Data availability

Data deposited in GEO under accession code GSE131136. Additional data are provided as source data files.

The following data sets were generated

Article and author information

Author details

  1. Lauren M Saunders

    Department of Genome Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4377-4252
  2. Abhishek K Mishra

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Andrew J Aman

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Victor M Lewis

    Department of Genome Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Matthew B Toomey

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9184-197X
  6. Jonathan S Packer

    Department of Genome Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Xiaojie Qiu

    Department of Genome Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jose L McFaline-Figueroa

    Department of Genome Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Joseph C Corbo

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9323-7140
  10. Cole Trapnell

    Department of Genome Sciences, University of Washington, Seattle, United States
    For correspondence
    coletrap@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
  11. David M Parichy

    Department of Biology, University of Virginia, Charlottesville, United States
    For correspondence
    dparichy@virginia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2771-6095

Funding

National Institute of General Medical Sciences (R35 GM122471)

  • David M Parichy

Eunice Kennedy Shriver National Institute of Child Health and Human Development (DP2 HD088158)

  • Cole Trapnell

National Eye Institute (EY024958)

  • Joseph C Corbo

W. M. Keck Foundation

  • Cole Trapnell

Alfred P. Sloan Foundation

  • Cole Trapnell

Paul G Allen Frontiers Group

  • Cole Trapnell

National Eye Institute (EY025196)

  • Joseph C Corbo

National Eye Institute (EY026672)

  • Joseph C Corbo

National Institute of General Medical Sciences (T32 GM007067)

  • Lauren M Saunders

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

Reviewing Editor

  1. Richard M White, Memorial Sloan Kettering Cancer Center, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (4170) of the University of Vriginia and (4094-01) of the University of Washington. For imaging and other procedures animals were anesthetized with MS222 or euthanized by overdose of MS222 and every effort was made to minimize suffering.

Version history

  1. Received: January 18, 2019
  2. Accepted: May 24, 2019
  3. Accepted Manuscript published: May 29, 2019 (version 1)
  4. Version of Record published: June 21, 2019 (version 2)

Copyright

© 2019, Saunders 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

  • 5,893
    views
  • 762
    downloads
  • 110
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Lauren M Saunders
  2. Abhishek K Mishra
  3. Andrew J Aman
  4. Victor M Lewis
  5. Matthew B Toomey
  6. Jonathan S Packer
  7. Xiaojie Qiu
  8. Jose L McFaline-Figueroa
  9. Joseph C Corbo
  10. Cole Trapnell
  11. David M Parichy
(2019)
Thyroid hormone regulates distinct paths to maturation in pigment cell lineages
eLife 8:e45181.
https://doi.org/10.7554/eLife.45181

Share this article

https://doi.org/10.7554/eLife.45181

Further reading

    1. Developmental Biology
    Zhimin Xu, Zhao Wang ... Yingchuan B Qi
    Research Article

    Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In C. elegans, the microRNA lin-4 critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation of lin-4 expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary for lin-4 activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with lin-4 expression timing. MYRF-1 regulates lin-4 expression cell-autonomously and hyperactive MYRF-1 can prematurely drive lin-4 expression in embryos and young first-stage larvae. The tandem lin-4 promoter DNA recruits MYRF-1GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly binds to the lin-4 promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of lin-4 expression.

    1. Developmental Biology
    2. Structural Biology and Molecular Biophysics
    Samuel C Griffiths, Jia Tan ... Hsin-Yi Henry Ho
    Research Article Updated

    The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, brachydactyly B, and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals.