Paraxis: A Basic Helix-Loop-Helix Protein Expressed in Paraxial Mesoderm and Developing Somites

Abstract

During vertebrate embryogenesis, cells from the paraxial mesoderm coalesce in a rostral-to-caudal progression to form the somites. Subsequent compartmentalization of the somites yields the sclerotome, myotome, and dermatome, which give rise to the axial skeleton, axial musculature, and dermis, respectively. Recently, we cloned a novel basic helix-loop-helix (bHLH) protein, called scleraxis, which is expressed in the sclerotome, in mesenchymal precursors of bone and cartilage, and in connective tissues. Here we report the cloning of a bHLH protein, called paraxis, which is nearly identical to scleraxis within the bHLH region but diverges in its amino and carboxyl termini. During mouse embryogenesis, paraxis transcripts are first detected at about Day 7.5 postcoitum within primitive mesoderm lying posterior to the head and heart primordia. Subsequently, paraxis expression progresses caudally through the paraxial mesoderm, immediately preceding somite formation. Paraxis is expressed at high levels in newly formed somites before the first detectable expression of the myogenic bHLH genes, and as the somite becomes compartmentalized, paraxis becomes downregulated in the myotome. Paraxis and scleraxis are coexpressed in the sclerotome, but paraxis expression declines soon after sclerotome formation, whereas scleroaxis expression increases in the sclerotome and its derivatives. The sequential expression of paraxis and scleraxis in the paraxial mesoderm and somites suggests that these bHLH proteins may comprise part of a regulatory pathway involved in patterning of the paraxial mesoderm and in the establishment of somitic cell lineages.

Scleraxis is Required for Differentiation of the Stapedius and Tensor Tympani Tendons of the Middle Ear

“…Moreover, normal auditory thresholds in Scx-null mice without otitis media suggest that Scx is not required for auditory function. However, functional redundancy cannot formally be ruled out as Paraxis (Burgess et al 1995), another member of the small Twist family of transcription factors that is required for somite formation and musculoskeletal patterning (Burgess et al 1996), and Hand1 and Hand2, members of the small Hand subfamily of bHLH transcription factors (Atchley and Fitch 1997;Firulli 2003) that regulate cardiac development (McFadden et al 2005), have significant sequence similarity to Scx and their expression has not been adequately defined in the mouse inner ear.…”

Establishment of the epaxial–hypaxial boundary in the avian myotome

“…The bHLH transcription factor Paraxis, which is required to establish and maintain the epithelial characteristics of the somite and to specify myogenic precursors in the dermomyotome (Burgess et al, 1995;Š ošic et al, 1997;Wilson-Rawls et al, 1999), was expressed throughout the dermomyotome, with up-regulated expression within the En1 domain and in all four dermomyotomal lips ( Fig. 1C-CЉ; weak expression is found in the myotome and sclerotome).…”

Molecular basis for skeletal variation: insights from developmental genetic studies in mice

“…Factors-Recently, two members of the bHLH transcription factor family were identified, paraxis and scleraxis, that display interesting expression patterns during somite development (Burgess et al, 1995;Cserjesi et al, 1995). Before the onset of somitogenesis, paraxis is weakly expressed in part of the primitive mesoderm.…”

“…Expression of paraxis continues throughout the uncompartimentalized epithelial somite. After compartimentalization, paraxis expression is shut down soon after myotome formation, and gradually declines in the other somite derivatives (Burgess et al, 1995). In paraxis mutants, somite formation is disrupted because mesodermal cells are unable to form epithelia.…”