Mustn1: A Developmentally Regulated Pan-Musculoskeletal Cell Marker and Regulatory Gene.

Michael Hadjiargyrou

doi:10.3390/ijms19010206

Abstract

The Mustn1 gene encodes a small nuclear protein (~9.6 kDa) that does not belong to any known family. Its genomic organization consists of three exons interspersed by two introns and it is highly homologous across vertebrate species. Promoter analyses revealed that its expression is regulated by the AP family of transcription factors, especially c-Fos, Fra-2 and JunD. Mustn1 is predominantly expressed in the major tissues of the musculoskeletal system: bone, cartilage, skeletal muscle and tendon. Its expression has been associated with normal embryonic development, postnatal growth, exercise, and regeneration of bone and skeletal muscle. Moreover, its expression has also been detected in various musculoskeletal pathologies, including arthritis, Duchenne muscular dystrophy, other skeletal muscle myopathies, clubfoot and diabetes associated muscle pathology. In vitro and in vivo functional perturbation revealed that Mustn1 is a key regulatory molecule in myogenic and chondrogenic lineages. This comprehensive review summarizes our current knowledge of Mustn1 and proposes that it is a new developmentally regulated pan-musculoskeletal marker as well as a key regulatory protein for cell differentiation and tissue growth.

Highlights

Tissues of the musculoskeletal system are all comprised of various cell types that exhibit individual differential gene expression patterns
A recent study with dogs, investigated whether systemic delivery of skeletal muscle-resident stem (MuStem) cells isolated from a 10-week-old healthy dog could serve as a therapeutic modality for the treatment of the Golden Retriever muscular dystrophy (GRMD) dog model, which is characterized by rapid progressive clinical dysfunction and severe muscle tissue remodeling [58]
It is abundantly clear that since our initial report on the cloning and expression studies of Mustn1 [5], a large number of studies implicate its expression with a role predominantly in tissues of the musculoskeletal system, as outlined

Summary

Introduction

Tissues of the musculoskeletal system (bone, cartilage, skeletal muscles, tendons, ligaments) are all comprised of various cell types that exhibit individual differential gene expression patterns. One of the genes identified in their screen was Mustn and displayed higher mRNA expression in broilers which instead exhibits rapid muscle growth than in layers, especially at two (~3-fold), four (~2.2-fold), six (~2.5-fold) and eight weeks (~1.5-fold), indicating that it plays a role in skeletal muscle hypertrophy. Based on these data, the authors concluded that Mustn mRNA/protein expression in chickens is most abundant in skeletal muscle and it is differentially regulated during post-hatch muscle growth and corroborating its role in muscle development [22]. 7 other genes with functions in the structural component of skeletal muscle were downregulated [25]

Exercise

Cartilage Expression Analyses

Functional Perturbation and Regulation

Disease States

Findings

Conclusions