Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Subject collections
    • Interviews
    • Sign up for alerts
  • About us
    • About DMM
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Outstanding paper prize
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contact
    • Contact DMM
    • Advertising
    • Feedback
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in

Search

  • Advanced search
Disease Models & Mechanisms
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Disease Models & Mechanisms

Advanced search

RSS   Twitter   Facebook   YouTube

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Subject collections
    • Interviews
    • Sign up for alerts
  • About us
    • About DMM
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Outstanding paper prize
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contact
    • Contact DMM
    • Advertising
    • Feedback
FIRST PERSON
First person – Zhaoyang Liu
Disease Models & Mechanisms 2019 12: dmm043612 doi: 10.1242/dmm.043612 Published 17 December 2019
  • Article
  • Figures & tables
  • Info & metrics
  • PDF
Loading

ABSTRACT

First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Zhaoyang Liu is first author on ‘Regulation of terminal hypertrophic chondrocyte differentiation in Prmt5 mutant mice modeling infantile idiopathic scoliosis’, published in DMM. Zhaoyang is a postdoctoral fellow in the lab of Ryan Gray at The University of Texas at Austin, Austin, TX, USA, investigating mechanisms of cartilage development and musculoskeletal-related diseases.

Embedded Image

Zhaoyang Liu

How would you explain the main findings of your paper to non-scientific family and friends?

Idiopathic scoliosis (IS) is an enigmatic disorder characterized by progressive curvature of the spine in otherwise healthy children, and is the most common type of musculoskeletal defect affecting children worldwide. The genetic causes of the disorder, particularly for infantile-onset IS, are not well defined. We set out to determine the role of the PRMT5 protein specifically in cartilaginous tissues in mouse using conditional genetics, which specifically remove gene function in a tissue of interest. We found that PRMT5 conditional mutant mice developed spine curvatures at 10 days of age and had reduced bone formation in the vertebral bodies and ribs, which recapitulates features of infantile IS. We further demonstrated that loss of Prmt5 in cartilaginous tissues affected key pathways and signaling important for chondrocyte differentiation and bone formation. Our study suggests that dysfunction of PRMT5 leading to impaired bone formation of the axial skeleton is a potential cause of infantile IS, and provides a useful animal model for future discovery of novel therapies for IS.

What are the potential implications of these results for your field of research?

Little is known about the cause of IS, which is largely due to a lack of valid animal models. In this study, we generated a conditional genetic mouse model that mimics human infantile IS, and links dysfunction of pathways and signaling important for chondrocyte differentiation and bone formation to infantile IS. We postulate a model where the onset of scoliosis is induced by asymmetric mechanical loading of the spine, as a result of subtle defects in bone formation during perinatal development. In light of these results, high-resolution, low-dose X-ray imaging and analysis of bone quality (bone mineral density) coupled with targeted sequence analysis of the PRMT5 locus in infantile IS patients is warranted.

What are the main advantages and drawbacks of the model system you have used as it relates to the disease you are investigating?

The main advantage of using the mouse model for our study is that it recapitulates the phenotype of infantile IS in humans. Distinct from congenital scoliosis, which is characterized by a failure of segmentation, formation or dysplasia in one or more vertebral units, IS patients do not display overt vertebral malformations. Our mouse model shows no spinal deformity during embryonic development, but rapidly develops scoliosis at neonatal stage, coupled with loss of bone formation in the ribcage and the spine. One main drawback of our mouse model is that these mutant mice are perinatal lethal, potentially due to respiratory distress caused by insufficient chest wall stiffness, which prevents us from further investigating the nature history of this disease.

“I was very excited when we found a novel regulator that plays a critical role during the terminal stage of chondrocyte differentiation and crosstalks with multiple master regulators of chondrogenesis.”

What has surprised you the most while conducting your research?

I was most surprised by how Prmt5 seems to precisely regulate cartilage and bone formation, by blocking flux of signaling and pathways important for hypertrophic chondrocyte differentiation. Chondrocyte differentiation has been extensively studied over the past decades and several master regulators have been described. I was very excited when we found a novel regulator that plays a critical role during the terminal stage of chondrocyte differentiation and crosstalks with multiple master regulators of chondrogenesis. Given that Prmt5 encodes a key epigenetic enzyme for symmetrical demethylation, I look forward to studying the direct molecular targets of this enzyme in cartilaginous tissues in the future.

Describe what you think is the most significant challenge impacting your research at this time and how will this be addressed over the next 10 years?

I think in the field of scoliosis research, the most significant challenge is the complexity of the etiology of this disease, and the lack of genetic animal models. The spine is a complex organ that contains various tissues, including cartilage, bone, connective tissues and innervation of the peripheral nervous system. In the next decades, the distinct and synergistic functions of these tissues that contribute to the pathogenesis of scoliosis should be addressed using different animal models, informed by new insights from human genetic studies of IS. These should also benefit from tissue-specific high-resolution transcriptomic and proteomic analyses of animal models of IS in the next 10 years.

Figure1
  • Download figure
  • Open in new tab
  • Download powerpoint

A 10-day-old Prmt5 mutant mouse develops scoliosis in the spine.

What changes do you think could improve the professional lives of early-career scientists?

I think changes in academia that can help improve the professional lives of early-career scientists include providing more fellowship and funding opportunities, and it would be very helpful if the ‘post-degree research experience’ eligibility of the applicant can be extended. The early stage of career development is very likely to overlap with many significant life events, so these changes can provide more opportunities and freedom for the grantees to focus on professional development.

What's next for you?

I will continue performing translational research in musculoskeletal-related diseases. Besides scoliosis, I'm also involved in several other research projects on musculoskeletal disorders, including intervertebral disc degeneration and osteoarthritis. I'm looking forward to becoming an investigator of musculoskeletal research after my postdoc training.

Footnotes

  • Zhaoyang Liu's contact details: Department of Pediatrics, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd, The University of Texas at Austin, Dell Medical School, Austin, TX 78723, USA. E-mail: zhaoyang.liu{at}austin.utexas.edu

  • © 2019. Published by The Company of Biologists Ltd
http://creativecommons.org/licenses/by/4.0

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Reference

  1. ↵
    1. Liu, Z.,
    2. Ramachandran, J.,
    3. Vokes, S. A. and
    4. Gray, R. S.
    (2019). Regulation of terminal hypertrophic chondrocyte differentiation in Prmt5 mutant mice modeling infantile idiopathic scoliosis. Dis. Model. Mech. 12, dmm041251. doi:10.1242/dmm.041251
    OpenUrlAbstract/FREE Full Text
Previous ArticleNext Article
Back to top
Previous ArticleNext Article

This Issue

RSSRSS

 Download PDF

Email

Thank you for your interest in spreading the word on Disease Models & Mechanisms.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
First person – Zhaoyang Liu
(Your Name) has sent you a message from Disease Models & Mechanisms
(Your Name) thought you would like to see the Disease Models & Mechanisms web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
FIRST PERSON
First person – Zhaoyang Liu
Disease Models & Mechanisms 2019 12: dmm043612 doi: 10.1242/dmm.043612 Published 17 December 2019
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
FIRST PERSON
First person – Zhaoyang Liu
Disease Models & Mechanisms 2019 12: dmm043612 doi: 10.1242/dmm.043612 Published 17 December 2019

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
    • ABSTRACT
    • Footnotes
    • Reference
  • Figures & tables
  • Info & metrics
  • PDF

Related articles

Cited by...

More in this TOC section

  • First person – Frederike Riemslagh
  • First person – Pranidhi Baddam
  • First person – Talia Nasr
Show more FIRST PERSON

Similar articles

Other journals from The Company of Biologists

Development

Journal of Cell Science

Journal of Experimental Biology

Biology Open

Advertisement

DMM and COVID-19

We are aware that the COVID-19 pandemic is having an unprecedented impact on researchers worldwide. The Editors of all The Company of Biologists’ journals have been considering ways in which we can alleviate concerns that members of our community may have around publishing activities during this time. Read about the actions we are taking at this time.

Please don’t hesitate to contact the Editorial Office if you have any questions or concerns.


Monica Justice bids farewell to DMM

In her farewell Editorial, outgoing Editor-in-Chief Monica Justice reminds us of the past half-decade of growth and of DMM's commitment to support the disease modelling community, concluding, “The knowledge and experience I gained during my time as Senior Editor and EiC at DMM is invaluable: working within a not-for-profit community publishing environment is a joy.”


3D imaging of beta cell mass in diabetic mouse models

In their inducible mouse model of diabetes, Roostalu et al. demonstrate how quantitative light-sheet imaging can capture changes in individual islets to help pharmacological research in diabetes.

Visit our YouTube channel to watch more videos from DMM, our sister journals and the Company.


Modelling Joubert syndrome patient-derived mutations in C. elegans

In this issue’s Editor’s choice, Karen Lange and colleagues used C. elegans to model and characterise two patient-derived mutations that cause the ciliopathy Joubert syndrome.


Interview – Karen Lange

First author of our current Editor’s choice, Karen Lange takes us behind the scenes of the paper, and shares her thoughts on how the lack of both time and job security will impact her research.

Articles

  • Accepted manuscripts
  • Issue in progress
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Subject collections
  • Interviews
  • Sign up for alerts

About us

  • About DMM
  • Editors and Board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Journal Meetings
  • Workshops
  • The Company of Biologists

For Authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • Biology Open transfer

Journal Info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Sign up for alerts

Contact

  • Contact DMM
  • Advertising
  • Feedback

Twitter   YouTube   LinkedIn

© 2021   The Company of Biologists Ltd   Registered Charity 277992