ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Morphogenesis and Patterning
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1639191
The Mkx-TGF-β pathway Induced the Development of the Myodural Bridge Complex in SD Rats
Provisionally accepted- 1Department of Anatomy, College of Basic Medicine, Dalian Medical University, Dalian, China
- 2Department of Radiology, Dalian University Affiliated Xinhua Hospital, Dalian, China
- 3Medical school, St George's University of London, London, United Kingdom
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective: The myodural bridge complex (MDBC) is a tendon-like structure highly conserved during vertebrate evolution, suggesting it plays an important physiological role. Substantial evidence indicates that the MDBC may contribute to cerebrospinal fluid (CSF) circulation by generating mechanical force. Studying its developmental process may offer new insights into CSF dynamics and lead to improved strategies for diagnosing and treating neurodegenerative diseases.This study utilized utilized lentiviral plasmids to either knockdown or overexpress the Mkx gene in newborn Sprague-Dawley rats (SD) rats, establishing three groups: control, overexpression group, and interference group. Suboccipital injections were performed at birth. Histological staining and qPCR were conducted at multiple time points to assess the morphological and genetic impacts of Mkx modulation on the development of the MDBC. Results: Transfection efficiency was confirmed by Green fluorescent protein (GFP) expression quantification, in vivo bioluminescent imaging, and Western blot validation in all experimental cohorts. Mkx knockdown exhibited diminished collagen fiber development accompanied by compensatory hyperplasia of occipital periosteum-derived fibrous tissues. Transcriptomic analysis revealed that Mkx overexpression upregulated tendon-related genes (Scx, Egr1) and downregulated myogenic regulators (Myod), with inverse expression patterns observed in knockdown models. Pathway gene analysis identified the TGF-β signaling cascade and associated mechanosensitive genes as central regulators of the MDBC. Conclusion: Mkx exerts bidirectional regulation on MDBC development by modulating the TGF-β signaling pathway. Overexpression of Mkx promotes collagen deposition and structural reinforcement in MDBC through coordinated molecular mechanisms: upregulating Scx/Egr1 expression, downregulating Myod, and inducing hyperplastic growth of deep fascial fibers in the rectus capitis dorsal minor muscle (RCDmi). Conversely, Mkx suppression maintains tissue integrity through three synergistic mechanisms: upregulating Myod expression, inducing MDBC fiber proliferation, and facilitating adaptive remodeling of the posterior atlanto-occipital membrane (PAOM). At the molecular level, Mkx coordinates differentiation processes through dynamic equilibrium of Scx/Egr1/Myod expression profiles while constructing regulatory networks that couple biomechanical-chemical signals via TGF-β pathway activation.
Keywords: CSF, Myodural Bridge Complex, MKX, TGF-β, developmental regulation
Received: 01 Jun 2025; Accepted: 10 Jul 2025.
Copyright: © 2025 Jiang, Li, Zhang, Sun, Shah, Li, Gilmore, Zhang and Sui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jian-Fei Zhang, Department of Anatomy, College of Basic Medicine, Dalian Medical University, Dalian, China
Hong-Jin Sui, Department of Anatomy, College of Basic Medicine, Dalian Medical University, Dalian, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.