Engrailed controls epaxial-hypaxial muscle innervation and the establishment of vertebrate three-dimensional mobility

Abstract

Engrailed controls epaxial-hypaxial muscle innervation and the establishment of vertebrate three-dimensional mobility, Developmental Biology, http://dx.doi.org/10. 1016/j.ydbio.2017.08.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractChordates are characterised by contractile muscle on either side of the body that promotes movement by side-to-side undulation. In the lineage leading to modern jawed vertebrates (crown group gnathostomes), this system was refined: body muscle became segregated into distinct dorsal (epaxial) and ventral (hypaxial) components that are separately innervated by the medial and hypaxial motors column, respectively, via the dorsal and ventral ramus of the spinal nerves. This allows full three-dimensional mobility, which in turn was a key factor in their evolutionary success.How the new gnathostome system is established during embryogenesis and how it may have evolved in the ancestors of modern vertebrates is not known.Vertebrate Engrailed genes have a peculiar expression pattern as they temporarily demarcate a central domain of the developing musculature at the epaxial-hypaxial boundary. Moreover, they are the only genes known with this particular expression pattern. The aim of this study was to investigate whether Engrailed genes control epaxial-hypaxial muscle development and innervation.Investigating chick, mouse and zebrafish as major gnathostome model organisms, we found that the Engrailed expression domain was associated with the establishment of the epaxial-hypaxial boundary of muscle in all three species. Moreover, the outgrowing epaxial and hypaxial nerves orientated themselves with respect to this Engrailed domain. In the chicken, loss and gain ofEngrailed function changed epaxial-hypaxial somite patterning. Importantly, in all animals studied, loss and gain of Engrailed function severely disrupted the pathfinding of the spinal motor axons, suggesting that Engrailed plays an evolutionarily conserved role in the separate innervation of vertebrate epaxial-hypaxial muscle.

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

“…The epaxial muscles are the intrinsic muscles of the back that are closely associated with the vertebral column and innervated by the dorsal rami of the spinal cord ventral roots, while the hypaxial muscles lie ventral to the vertebrae and are innervated by the ventral rami (Fetcho, 1987). This division of axial muscle into two separately innervated muscles increased the range of motion, allowing for both lateral undulations and dorsal-ventral flexion in the earliest vertebrates (Ahmed et al, 2017). Subsequently in jawed vertebrates, epaxial and hypaxial muscles became further functionally separated, as a horizontal septum of connective tissue developed between these muscles (Figure 1D; reviewed in Wotton et al, 2015).…”

“…Ultimately, the dorsomedial lip of the dermomyotome and the medial myotome give rise to the epaxial muscles, while the ventrolateral lip of the dermomyotome and the lateral myotome give rise to the hypaxial muscles (Figure 3A-C; Cinnamon et al, 1999; Denetclaw et al, 1997; Gros et al, 2004; Pu et al, 2013). On a molecular level, the transcription factor, Engrailed , appears to be essential for establishing the boundary between the epaxial and hypaxial muscle domains (Ahmed et al, 2017; Wotton et al, 2015). …”

Neural crest and the patterning of vertebrate craniofacial muscles

“…In somites, the boundary of En‐2 expression marks the site of demarcation separating epaxial from hypaxial muscles. This separation is accompanied by differential innervation of these groups by dorsal and ventral branches of spinal nerves, and is proposed as an evolutionary gnathostome synapomorphy that allowed for extension‐flexion as well as side‐to‐side movements of the vertebral column (Ahmed et al, ).…”

Stepwise participation of HGF/MET signaling in the development of migratory muscle precursors during vertebrate evolution

“…The vertebrate skeletal musculature can be divided into two major categories: cranial muscles derived from head mesoderm, and trunk muscles that originate from somites. In gnathostomes, the trunk muscles are further divided into two groups: epaxial muscles, innervated by the dorsal ramus of the spinal nerve and located dorsal to the horizontal myoseptum, and hypaxial muscles, which are innervated by the ventral ramus of the spinal nerve and situated ventral to the myoseptum [ 1 – 4 ].…”