Requirement of the paraxis gene for somite formation and musculoskeletal patterning

Abstract

The segmental organization of the vertebrate embryo is first apparent when somites form in a rostrocaudal progression from the paraxial mesoderm adjacent to the neural tube. Newly formed somites appear as paired epithelial spheres that become patterned to form vertebrae, ribs, skeletal muscle and dermis. Paraxis is a basic helix-loop-helix transcription factor expressed in paraxial mesoderm and somites. Here we show that in mice homozygous for a paraxis null mutation, cells from the paraxial mesoderm are unable to form epithelia and so somite formation is disrupted. In the absence of normal somites, the axial skeleton and skeletal muscle form but are improperly patterned. Unexpectedly, however, we found that formation of epithelial somites was not required for segmentation of the embryo or for the establishment of somitic cell lineages. These results demonstrate that paraxis regulates somite morphogenesis, and that the function of somites is to pattern the axial skeleton and skeletal muscles.

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.…”

From segment to somite: Segmentation to epithelialization analyzed within quantitative frameworks

“…In most vertebrates, subgroups of mesenchymal cells dynamically alter their shape to form an outer epithelial layer enclosing a mesenchymal core (Duband et al, 1987). This mesenchymal-to-epithelial transition (MET) of cells within a somite is distinct from the segment border formation, as was shown by the knockdown of Paraxis in mouse (Burgess et al, 1996). Paraxis is likely regulated in part by ectodermal and neural tube derived signals (Sosic et al, 1997;Schmitt et al, 2004), and its expression is a consistent marker for the onset of the epithelialization process.…”

Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome

“…Mesp2 is involved in the Notch signaling pathway and is needed for the initiation of somitogenesis and the specification of the anterior half of the somite (Burgess et al, 1996). The expression domain of Mesp2 in the recently formed presumptive somite (Ϫ2) was reduced in the mutant, indicating that fewer cells are available for the formation of somites (Fig.…”

“…Paraxis is needed for the formation of epithelial somites and in Paraxis-null mice no epithelia form in the paraxial mesoderm (Burgess et al, 1996). Epithelialization defects subsequently lead to a perturbed formation of the sclerotome in differentiating somites as seen by misexpression of Pax9, Tbx18, and Uncx4.1.…”