Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues

Abstract

In vertebrates, head and trunk muscles develop from different mesodermal populations and are regulated by distinct genetic networks. Neck muscles at the head-trunk interface remain poorly defined due to their complex morphogenesis and dual mesodermal origins. Here, we use genetically modified mice to establish a 3D model that integrates regulatory genes, cell populations and morphogenetic events that define this transition zone. We show that the evolutionary conserved cucullaris-derived muscles originate from posterior cardiopharyngeal mesoderm, not lateral plate mesoderm, and we define new boundaries for neural crest and mesodermal contributions to neck connective tissue. Furthermore, lineage studies and functional analysis of Tbx1- and Pax3-null mice reveal a unique genetic program for somitic neck muscles that is distinct from that of somitic trunk muscles. Our findings unveil the embryological and developmental requirements underlying tetrapod neck myogenesis and provide a blueprint to investigate how muscle subsets are selectively affected in some human myopathies.

Anterior trunk muscle shows mix of axial and appendicular developmental patterns

“…The anterior six somites all up‐regulate expression of genes associated with MMPs at their ventral margins, but cells from these somites differentiate at very different times after this expression. Our work supports the hypothesis that the PHM has characteristics of both primaxial and abaxial muscles, similar to some extrinsic shoulder muscles in amniotes . The intermediate nature of PHM development reflects its unique characteristic of bridging the somite‐derived axial skeleton, and the almost entirely LPM‐derived appendicular skeleton …”

“…Our work supports the hypothesis that the PHM has characteristics of both primaxial and abaxial muscles, similar to some extrinsic shoulder muscles in amniotes. 8,10 The intermediate nature of PHM development reflects its unique characteristic of bridging the somite-derived axial skeleton, and the almost entirely LPM-derived appendicular skeleton. 10,35,36 The PHM is unlike MMP-derived muscles in the context and the timing of its differentiation.…”

“…Therefore, axial muscles are primaxial, because the connective tissue cells within the muscle are derived from somitic cells . In contrast, muscles associated with the pectoral appendage develop from cells which arise in the somites and then migrate to a distant site before differentiation . The migratory muscle precursors (MMPs) that form these muscles move into the lateral plate mesoderm (LPM).…”

“…5 In contrast, muscles associated with the pectoral appendage develop from cells which arise in the somites and then migrate to a distant site before differentiation. [6][7][8][9] The migratory muscle precursors (MMPs) that form these muscles move into the lateral plate mesoderm (LPM). Therefore, the appendicular muscles are abaxial, because the connective tissue cells within these muscles are derived from LPM.…”

Connecting muscle development, birth defects, and evolution: An essential role for muscle connective tissue

“…The neural crest is a migratory population derived from the dorsal neural tube and not only give rises to the head’s MCT, but also the tendons, facial bones, many bones of the skull (Couly et al, 1993; Noden, 1983b; Olsson et al, 2001; Piekarski et al, 2014). Unlike the true head muscles, the neck muscles and MCT represent a transitional region in which muscle derives from somites and cranial mesoderm and MCT derives from neural crest and the lateral plate mesoderm (Durland et al, 2008; Heude et al, 2018; Lescroart et al, 2015; Matsuoka et al, 2005; Piekarski and Olsson, 2007; Sefton et al, 2016; Theis et al, 2010). …”