1. Developmental Biology
  2. Evolutionary Biology
Download icon

Selection for increased tibia length in mice alters skull shape through parallel changes in developmental mechanisms

Research Article
  • Cited 0
  • Views 140
  • Annotations
Cite this article as: eLife 2021;10:e67612 doi: 10.7554/eLife.67612
Voice your concerns about research culture and research communication: Have your say in our 7th annual survey.

Abstract

Bones in the vertebrate cranial base and limb skeleton grow by endochondral ossification, under the control of growth plates. Mechanisms of endochondral ossification are conserved across growth plates, which increases covariation in size and shape among bones, and in turn may lead to correlated changes in skeletal traits not under direct selection. We used micro-CT and geometric morphometrics to characterize shape changes in the cranium of the Longshanks mouse, which was selectively bred for longer tibiae. We show that Longshanks skulls became longer, flatter, and narrower in a stepwise process. Moreover, we show that these morphological changes likely resulted from developmental changes in the growth plates of the Longshanks cranial base, mirroring changes observed in its tibia. Thus, indirect and non-adaptive morphological changes can occur due to developmental overlap among distant skeletal elements, with important implications for interpreting the evolutionary history of vertebrate skeletal form.

Data availability

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

Article and author information

Author details

  1. Colton Michael Unger

    Biological Sciences, University of Calgary, Calgary, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Jay Devine

    Anatomy and Cell Biology, University of Calgary, Calgary, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Benedikt Hallgrímsson

    Anatomy and Cell Biology, University of Calgary, Calgary, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Campbell Rolian

    Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Canada
    For correspondence
    cprolian@ucalgary.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7242-342X

Funding

Natural Sciences and Engineering Research Council of Canada (Discovery Grant 4181932)

  • Campbell Rolian

University of Calgary (Faculty of Veterinary Medicine)

  • Campbell Rolian

Natural Sciences and Engineering Research Council of Canada (Canada Graduate Scholarship - Masters)

  • Colton Michael Unger

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 animal procedures were approved by the Health Sciences Animal Care Committee at the University of Calgary (Protocols AC13-0077 and AC17-0026) and performed in accordance with best practices outlined by the Canadian Council on Animal Care.

Reviewing Editor

  1. George H Perry, Pennsylvania State University, United States

Publication history

  1. Received: February 18, 2021
  2. Accepted: April 23, 2021
  3. Accepted Manuscript published: April 26, 2021 (version 1)

Copyright

© 2021, Unger 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

  • 140
    Page views
  • 24
    Downloads
  • 0
    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)

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. Developmental Biology
    2. Plant Biology
    Elvira Hernandez-Lagana et al.
    Research Article

    In multicellular organisms, sexual reproduction requires the separation of the germline from the soma. In flowering plants, the female germline precursor differentiates as a single spore mother cell (SMC) as the ovule primordium forms. Here, we explored how organ growth contributes to SMC differentiation. We generated 92 annotated 3D images at cellular resolution in Arabidopsis. We identified the spatio-temporal pattern of cell division that acts in a domain-specific manner as the primordium forms. Tissue growth models uncovered plausible morphogenetic principles involving a spatially confined growth signal, differential mechanical properties, and cell growth anisotropy. Our analysis revealed that SMC characteristics first arise in more than one cell but SMC fate becomes progressively restricted to a single cell during organ growth. Altered primordium geometry coincided with a delay in the fate restriction process in katanin mutants. Altogether, our study suggests that tissue geometry channels reproductive cell fate in the Arabidopsis ovule primordium.

    1. Cancer Biology
    2. Developmental Biology
    Rediet Zewdu et al.
    Research Article Updated

    Cancer cells undergo lineage switching during natural progression and in response to therapy. NKX2-1 loss in human and murine lung adenocarcinoma leads to invasive mucinous adenocarcinoma (IMA), a lung cancer subtype that exhibits gastric differentiation and harbors a distinct spectrum of driver oncogenes. In murine BRAFV600E-driven lung adenocarcinoma, NKX2-1 is required for early tumorigenesis, but dispensable for established tumor growth. NKX2-1-deficient, BRAFV600E-driven tumors resemble human IMA and exhibit a distinct response to BRAF/MEK inhibitors. Whereas BRAF/MEK inhibitors drive NKX2-1-positive tumor cells into quiescence, NKX2-1-negative cells fail to exit the cell cycle after the same therapy. BRAF/MEK inhibitors induce cell identity switching in NKX2-1-negative lung tumors within the gastric lineage, which is driven in part by WNT signaling and FoxA1/2. These data elucidate a complex, reciprocal relationship between lineage specifiers and oncogenic signaling pathways in the regulation of lung adenocarcinoma identity that is likely to impact lineage-specific therapeutic strategies.