- ReportMET mutation causes muscular dysplasia and arthrogryposis
- Hang Zhou1,2,3,4,†,
- Chengjie Lian1,2,3,4,†,
- Tingting Wang1,
- Xiaoming Yang1,
- Caixia Xu5,
- Deying Su1,
- Shuhui Zheng5,
- Xiangyu Huang6,
- Zhiheng Liao1,
- Taifeng Zhou1,
- Xianjian Qiu7,
- Yuyu Chen1,
- Bo Gao7,
- Yongyong Li5,
- Xudong Wang7,
- Guoling You8,
- Qihua Fu8,
- Christina Gurnett9,10,11,
- Dongsheng Huang7 and
- Peiqiang Su (supq{at}mail.sysu.edu.cn)*,1,2,3,4,12
- 1Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat‐sen University, Guangzhou, Guangdong, China
- 2Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat‐sen University, Guangzhou, Guangdong, China
- 3Guangdong Province Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong, China
- 4Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication, Guangzhou, Guangdong, China
- 5Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat‐sen University, Guangzhou, Guangdong, China
- 6Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
- 7Department of Spine Surgery, Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University, Guangzhou, Guangdong, China
- 8Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 9Department of Orthopaedic Surgery, Washington University, St. Louis, MO, USA
- 10Department of Neurology, Washington University, St. Louis, MO, USA
- 11Department of Pediatrics, Washington University, St. Louis, MO, USA
- 12Present Address: Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat‐sen University, Guangzhou, Guangdong, China
- ↵*Corresponding author. Tel: +862087755766 6236; E‐mail: supq{at}mail.sysu.edu.cn
↵† These authors contributed equally to this work
In this study, MET was identified as a causative gene for arthrogryposis, characterized by congenital contractures of two or more parts of the body. The mutant MET p.Y1234C impaired activation of MET tyrosine kinase, resulting in muscular dysplasia of the limbs.
Synopsis
In this study, MET was identified as a causative gene for arthrogryposis, characterized by congenital contractures of two or more parts of the body. The mutant MET p.Y1234C impaired activation of MET tyrosine kinase, resulting in muscular dysplasia of the limbs.
MET p.Y1234C mutation was identified in a four‐generation arthrogryposis pedigree.
Muscular dysplasia of the upper arms and hands was observed in the arthrogryposis patients.
In vitro, MET p.Y1234C was responsible for the failure in MET tyrosine kinase activation.
In vivo, Met p.Y1232C led to defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts.
EMBO Mol Med (2019) e9709
- Received August 21, 2018.
- Revision received January 28, 2019.
- Accepted January 29, 2019.
- © 2019 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- OpinionInnovation and competition in advanced therapy medicinal products
Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy and tissue engineering products, represent a paradigm shift in health care, but they are expensive. E. Seoane‐Vazquez, V. Shukla and R. Rodriguez‐Monguio discuss ATMPs prospects for the generics market.
EMBO Mol Med (2019) e9992
- © 2019 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Research ArticleTargeting miR‐34a/Pdgfra interactions partially corrects alveologenesis in experimental bronchopulmonary dysplasia
- Jordi Ruiz‐Camp1,2,
- Jennifer Quantius2,
- Ettore Lignelli1,2,
- Philipp F Arndt2,
- Francesco Palumbo1,2,
- Claudio Nardiello1,2,
- David E Surate Solaligue1,2,
- Elpidoforos Sakkas1,2,4,
- Ivana Mižíková1,2,5,
- José Alberto Rodríguez‐Castillo1,2,
- István Vadász2,
- William D Richardson3,
- Katrin Ahlbrecht1,2,
- Susanne Herold2,
- Werner Seeger1,2 and
- Rory E Morty (rory.morty{at}mpi-bn.mpg.de)*,1,2
- 1Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Bad Nauheim, Germany
- 2Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany
- 3Wolfson Institute for Biomedical Research, University College London, London, UK
- 4Present Address: Department of Clinical Genomics, SciLifeLab, Stockholm, Sweden
- 5Present Address: Regenerative Medicine Program, Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- ↵*Corresponding author. Tel: +49 6032 705 271; Fax: +49 6032 705 471; E‐mail: rory.morty{at}mpi-bn.mpg.de
The pathogenic mechanisms underlying stunted lung development associated with bronchopulmonary dysplasia (BPD) are unknown. In this study, the interaction between miR 34a and the Pdgfra 3′‐UTR was validated as both a causal factor and a potentially “druggable” target in BPD driven by oxygen toxicity.
Synopsis
The pathogenic mechanisms underlying stunted lung development associated with bronchopulmonary dysplasia (BPD) are unknown. In this study, the interaction between miR 34a and the Pdgfra 3′‐UTR was validated as both a causal factor and a potentially “druggable” target in BPD driven by oxygen toxicity.
miR‐34a expression was increased by elevated oxygen levels in PDGFRα+ cells.
PDGFRα expression was negatively regulated by miR‐34a in vitro and in vivo.
Lung development was protected by genetic ablation of miR‐34a expression in PDGFRα+ cells in vivo.
PDGFRα+ cell abundance was partially restored by neutralization of miR‐34a using LNA antimiRs in developing lungs.
Disrupting the miR‐34a/Pdgfra mRNA interaction revealed a new pathogenic pathway that could be pharmacologically manipulated.
EMBO Mol Med (2019) e9448
- Received June 16, 2018.
- Revision received January 19, 2019.
- Accepted January 22, 2019.
- © 2019 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Louis‐Jeantet Prize Winner: ReviewGenetic engineering of hematopoiesis: current stage of clinical translation and future perspectives
- 1San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Hospital and Research Institute, “Vita ‐ Salute San Raffaele” University Medical School, Milan, Italy
- ↵*Corresponding author. Tel: +39 02 2643 4682; E‐mail: naldini.luigi{at}hsr.it
The 2019 Louis‐Jeantet Prize for Medicine winner Luigi Naldini offers here a very comprehensive and interesting review on gene therapy in general and hematopoietic stem cell gene therapy in particular, with a specific emphasis on clinical applications.
EMBO Mol Med (2019) e9958
- Received January 2, 2019.
- Revision received January 3, 2019.
- Accepted January 7, 2019.
- © 2019 The Author. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Louis‐Jeantet Prize Winner: ReviewThe first steps in vision: cell types, circuits, and repair
The 2019 Louis‐Jeantet Prize for Medicine winner Botond Roska provides a motivating account of his work on the basic principles of visual information processing, leading to the development of therapeutic strategies for retinal disorders.
EMBO Mol Med (2019) e10218
- Received December 17, 2018.
- Revision received January 2, 2019.
- Accepted January 3, 2019.
- © 2019 The Author. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
