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Individual Limb Muscle Bundles Are Formed through Progressive Steps Orchestrated by Adjacent Connective Tissue Cells during Primary Myogenesis

Research output: Contribution to journalArticle

Laurianne Besse, Caroline J. Sheeba, Mark Holt, Maurice Labuhn, Susan Wilde, Eleanor Feneck, Donald Bell, Ania Kucharska, Malcolm P.O. Logan

Original languageEnglish
Pages (from-to)3552-3565.e6
JournalCell Reports
Volume30
Issue number10
Early online date10 Mar 2020
DOIs
Publication statusE-pub ahead of print - 10 Mar 2020

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Abstract

Although the factors regulating muscle cell differentiation are well described, we know very little about how differentiating muscle fibers are organized into individual muscle tissue bundles. Disruption of these processes leads to muscle hypoplasia or dysplasia, and replicating these events is vital in tissue engineering approaches. We describe the progressive cellular events that orchestrate the formation of individual limb muscle bundles and directly demonstrate the role of the connective tissue cells that surround muscle precursors in controlling these events. We show how disruption of gene activity within or genetic ablation of connective tissue cells impacts muscle precursors causing disruption of muscle bundle formation and subsequent muscle dysplasia and hypoplasia. We identify several markers of the populations of connective tissue cells that surround muscle precursors and provide a model for how matrix-modifying proteoglycans secreted by these cells may influence muscle bundle formation by effects on the local extracellular matrix (ECM) environment.

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