Chapter One - Craniofacial Muscle Development

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Abstract

The developmental mechanisms that control head muscle formation are distinct from those that operate in the trunk. Head and neck muscles derive from various mesoderm populations in the embryo and are regulated by distinct transcription factors and signaling molecules. Throughout the last decade, developmental, and lineage studies in vertebrates and invertebrates have revealed the peculiar nature of the pharyngeal mesoderm that forms certain head muscles and parts of the heart. Studies in chordates, the ancestors of vertebrates, revealed an evolutionarily conserved cardiopharyngeal field that progressively facilitates the development of both heart and craniofacial structures during vertebrate evolution. This ancient regulatory circuitry preceded and facilitated the emergence of myogenic cell types and hierarchies that exist in vertebrates. This chapter summarizes studies related to the origins, signaling circuits, genetics, and evolution of the head musculature, highlighting its heterogeneous characteristics in all these aspects, with a special focus on the FGF–ERK pathway. Additionally, we address the processes of head muscle regeneration, and the development of stem cell-based therapies for treatment of muscle disorders.

Section snippets

Head Muscle Formation and Heterogeneity: Extraocular Muscles, Pharyngeal Mesoderm, and Neck Muscles

Muscles in the head are highly heterogeneous with respect to both origin and regulatory mechanisms. This section summarizes the different mesoderm tissues that contribute to the formation of the head muscles, presented here in the order from caudal to rostral. The human head contains more than 60 muscles, which control eye movements, food uptake, respiration, and facial expression (Bothe et al., 2007, Diogo et al., 2015, Grifone and Kelly, 2007, Noden and Francis-West, 2006, Sambasivan et al.,

Overlap Between Cardiac and Pharyngeal Muscle Progenitors

A strong link between the evolution of head muscles and the heart has been revealed in recent years. Both muscle cell types are formed by a common pool of mesoderm progenitor cells within the cardiopharyngeal field (CPF) of vertebrate embryos. The origin of this field could be traced back in evolution to chordates, the sister group to the vertebrates (Diogo et al., 2015).

PM cells give rise to both pharyngeal muscles and cardiac progenitors depending upon signals from adjacent pharyngeal

Fibroblast Growth Factor Signaling

Fibroblast growth factors (FGFs) are polypeptide growth factors with diverse biological activities. The FGF family is comprised of at least 22 members, which act predominantly via a set of tyrosine kinase receptors (FGFR 1–4). Binding of FGF to its receptor induces receptor dimerization, with subsequent activation of the cytoplasmic tyrosine kinase domain followed by intermolecular transphosphorylation and activation of downstream signaling events. This activation induces different cellular

Head Muscle Regeneration

To date, investigation of muscle regeneration has focused largely on trunk/limb skeletal muscles only. There have been several clinical trials aimed at testing safety and efficacy of stem cell-based therapies to treat skeletal muscle injury, muscular dystrophy, and myocardial infarction. Yet, advances in the field of craniofacial skeletal muscle regeneration remain behind the curve. Approaches to skeletal muscle regenerative medicine have concentrated on the use of growth factors, satellite

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