Biology subjects

Goh, Q.

Publications and source records attributed to Goh, Q..

3 recordsLinked to original sources

bioRxiv2026

Elucidating the JNK Signaling Pathway in Neonatal Muscle Growth and Neuromuscular Contractures

Neuromuscular contractures arising from neonatal brachial plexus injuries (NBPI) are highly disabling and currently incurable. We previously showed that contractures involve impaired longitudinal growth of denervated muscles, a defect mediated through myostatin (MSTN) signaling, a potent negative regulator of muscle size. However, MSTN-mediated contractures occur independent of canonical signaling pathways, including SMAD 2/3 and AKT/mTOR. Through a mouse model of NBPI, our present study extended these findings by revealing pharmacologic inhibition of JNK signaling, a noncanonical pathway downstream of MSTN, partially rescues contractures without restoring muscle length. Rather, JNK activation upregulates myofiber expression of the target gene Lmna, which encodes the nuclear envelope proteins Lamin A and Lamin C that are vital for nuclear stability, resulting in pervasive myonuclear displacement. These results suggest that other factors contribute to contracture pathology beyond deficits in longitudinal muscle growth. Further, while JNK inhibition does not restore length of denervated muscles, it impedes size and mass of normally innervated neonatal muscles, suggesting a requirement of JNK signaling for neonatal muscle growth. Our collective findings thereby establish new mechanistic insights into the molecular basis of aberrant muscle growth and neuromuscular contracture formation, potentially leading to novel targets for muscle restorative strategies and medical contracture prevention.

developmental biology↗

bioRxiv2023

The Role of Sympathetic Innervation in Neonatal Muscle Growth and Neuromuscular Contractures

Neonatal brachial plexus injury (NBPI), a leading cause of pediatric upper limb paralysis, results in disabling and incurable muscle contractures that are driven by impaired longitudinal growth of denervated muscles. A rare form of NBPI, which maintains both afferent and sympathetic muscle innervation despite motor denervation, protects against contractures. We have previously ruled out a role for NRG/ErbB signaling, the predominant pathway governing antegrade afferent neuromuscular transmission, in modulating the formation of contractures. Our current study therefore investigated the contributions of sympathetic innervation of skeletal muscle in modulating NBPI-induced contractures. Through chemical sympathectomy and pharmacologic modification with a {beta}2-adrenergic agonist, we discovered that sympathetic innervation alone is neither required nor sufficient to modulate contracture formation in neonatal mice. Despite this, sympathetic innervation plays an intriguing sex-specific role in mediating neonatal muscle growth, as the cross-sectional area (CSA) and volume of normally innervated male muscles were diminished by ablation of sympathetic neurons and increased by {beta}-adrenergic stimulation. Intriguingly, the robust alterations in CSA occurred with minimal changes to normal longitudinal muscle growth as determined by sarcomere length. Instead, {beta}-adrenergic stimulation exacerbated sarcomere overstretch in denervated male muscles, indicating potentially discrete regulation of muscle width and length. Future investigations into the mechanistic underpinnings of these distinct aspects of muscle growth are thus essential for improving clinical outcomes in patients affected by muscle disorders in which both length and width are affected.

developmental biology↗

bioRxiv2017

Myomerger Induces Fusion Of Non-Fusogenic Cells And Is Required For Myoblast Fusion

Despite the importance of cell fusion for mammalian development and physiology, the factors critical for this process remain to be fully defined1. This lack of knowledge has severely limited our ability to reconstitute cell fusion, which is necessary to decipher the biochemical mechanisms driving plasma membrane merger. Myomaker (Tmem8c) is a muscle-specific protein required for myoblast fusion2,3. Expression of myomaker in fibroblasts drives their fusion with myoblasts, but not with other myomaker-fibroblasts, highlighting the requirement of additional myoblast-derived factors for fusion. Here, we demonstrate that Gm7325, named myomerger, induces the fusion of myomaker-expressing fibroblasts. Cell mixing experiments reveal that while myomaker renders cells fusion-competent, myomerger induces fusogenicity. Thus, myomaker and myomerger confer fusogenic activity to normally non-fusogenic cells. Myomerger is skeletal muscle-specific and only expressed during developmental and regenerative myogenesis. Disruption of myomerger in myoblast cell lines through Cas9-mutagenesis generated non-fusogenic myocytes. Genetic deletion of myomerger in mice results in a paucity of muscle fibers demonstrating a requirement for myomerger in normal muscle formation. Myomerger deficient myocytes exhibit an ability to differentiate and harbor organized sarcomeres, however remain mono-nucleated. These data identify myomerger as a fundamental myoblast fusion protein and establishes a system that begins to reconstitute mammalian cell fusion.

developmental biology↗