Divergent mechanisms regulate conserved cardiopharyngeal development and gene expression in distantly related ascidians

  1. Alberto Stolfi
  2. Elijah K Lowe
  3. Claudia Racioppi
  4. Filomena Ristoratore
  5. C Titus Brown
  6. Billie J Swalla
  7. Lionel Christiaen  Is a corresponding author
  1. New York University, United States
  2. Michigan State University, United States
  3. Stazione Zoologica Anton Dohrn, Italy
  4. University of Washington, United States

Abstract

Ascidians present a striking dichotomy between conserved phenotypes and divergent genomes: embryonic cell lineages and gene expression patterns are conserved between distantly related species. Much research has focused on Ciona or Halocynthia spp. but development in other ascidians remains poorly characterized. Here we surveyed the multipotent myogenic B7.5 lineage in Molgula spp. Comparisons to the homologous lineage in Ciona revealed identical cell division and fate specification events that result in segregation of larval, cardiac, and pharyngeal muscle progenitors. Moreover, the expression patterns of key regulators are conserved, but cross-species transgenic assays uncovered incompatibility, or "unintelligibility", of orthologous cis-regulatory sequences between Molgula and Ciona. These sequences drive identical expression patterns that are not recapitulated in cross-species assays. We show that this unintelligibility is likely due to changes in both cis- and trans-actingelements, hinting at widespread and frequent turnover of regulatory mechanisms underlying otherwise conserved aspects of ascidian embryogenesis.

Article and author information

Author details

  1. Alberto Stolfi

    New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Elijah K Lowe

    Michigan State University, East Lansing, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Claudia Racioppi

    Stazione Zoologica Anton Dohrn, Napoli, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Filomena Ristoratore

    Stazione Zoologica Anton Dohrn, Napoli, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. C Titus Brown

    Michigan State University, East Lansing, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Billie J Swalla

    University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Lionel Christiaen

    New York University, New York, United States
    For correspondence
    lc121@nyu.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Margaret Buckingham, Institut Pasteur, France

Publication history

  1. Received: June 18, 2014
  2. Accepted: September 5, 2014
  3. Accepted Manuscript published: September 10, 2014 (version 1)
  4. Version of Record published: September 30, 2014 (version 2)

Copyright

© 2014, Stolfi 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

  • 3,001
    Page views
  • 213
    Downloads
  • 54
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, 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. Alberto Stolfi
  2. Elijah K Lowe
  3. Claudia Racioppi
  4. Filomena Ristoratore
  5. C Titus Brown
  6. Billie J Swalla
  7. Lionel Christiaen
(2014)
Divergent mechanisms regulate conserved cardiopharyngeal development and gene expression in distantly related ascidians
eLife 3:e03728.
https://doi.org/10.7554/eLife.03728

Further reading

    1. Developmental Biology
    Tsz Long Chu, Peikai Chen ... Kathryn Song Eng Cheah
    Research Article Updated

    Bone homeostasis is regulated by hormones such as parathyroid hormone (PTH). While PTH can stimulate osteo-progenitor expansion and bone synthesis, how the PTH-signaling intensity in progenitors is controlled is unclear. Endochondral bone osteoblasts arise from perichondrium-derived osteoprogenitors and hypertrophic chondrocytes (HC). We found, via single-cell transcriptomics, that HC-descendent cells activate membrane-type 1 metalloproteinase 14 (MMP14) and the PTH pathway as they transition to osteoblasts in neonatal and adult mice. Unlike Mmp14 global knockouts, postnatal day 10 (p10) HC lineage-specific Mmp14 null mutants (Mmp14ΔHC) produce more bone. Mechanistically, MMP14 cleaves the extracellular domain of PTH1R, dampening PTH signaling, and consistent with the implied regulatory role, in Mmp14ΔHC mutants, PTH signaling is enhanced. We found that HC-derived osteoblasts contribute ~50% of osteogenesis promoted by treatment with PTH 1–34, and this response was amplified in Mmp14ΔHC. MMP14 control of PTH signaling likely applies also to both HC- and non-HC-derived osteoblasts because their transcriptomes are highly similar. Our study identifies a novel paradigm of MMP14 activity-mediated modulation of PTH signaling in the osteoblast lineage, contributing new insights into bone metabolism with therapeutic significance for bone-wasting diseases.

    1. Biochemistry and Chemical Biology
    2. Developmental Biology
    Zengdi Zhang, Zan Huang ... Hai-Bin Ruan
    Research Article Updated

    In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche.