The paired homeobox gene Uncx4.1 specifies pedicles, transverse processes and proximal ribs of the vertebral column

Abstract

The axial skeleton develops from the sclerotome, a mesenchymal cell mass derived from the ventral halves of the somites, segmentally repeated units located on either side of the neural tube. Cells from the medial part of the sclerotome form the axial perichondral tube, which gives rise to vertebral bodies and intervertebral discs; the lateral regions of the sclerotome will form the vertebral arches and ribs. Mesenchymal sclerotome cells condense and differentiate into chondrocytes to form a cartilaginous pre-skeleton that is later replaced by bone tissue. Uncx4.1 is a paired type homeodomain transcription factor expressed in a dynamic pattern in the somite and sclerotome. Here we show that mice homozygous for a targeted mutation of the Uncx4.1 gene die perinatally and exhibit severe malformations of the axial skeleton. Pedicles, transverse processes and proximal ribs, elements derived from the lateral sclerotome, are lacking along the entire length of the vertebral column. The mesenchymal anlagen for these elements are formed initially, but condensation and chondrogenesis do not occur. Hence, Uncx4.1 is required for the maintenance and differentiation of particular elements of the axial skeleton.

DNA methylation clocks for clawed frogs reveal evolutionary conservation of epigenetic ageing

“…Table 2 ). Human UNCX encodes a homeobox transcription factor whose mouse homolog is implicated the development of the axial skeleton and in neural progenitor regulation in the olfactory epithelium [61, 62] and for which increased DNAme (cg04816311) is associated with target organ damage in older African Americans [63]. Notably, mutations in the uncx orthologue in C. elegans, unc4 , extends male lifespan [64].…”

Spatial transcriptomics reveals a conserved segment polarity program that governs muscle patterning inNematostella vectensis

“…In protostomes, Uncx function is largely restricted to the nervous system, where it specifies motor neuron identity, sometimes in a repeated, segmentally polarized fashion (Cho and Park, 2008; Lacin et al, 2020; Miller et al, 1992; Walthall, 1995). In contrast, the mammalian Unc-4 homolog Uncx4.1 serves as one of the best characterized posterior identity markers of the developing somites, where it instructs the formation of distal ribs, transverse processes and pedicles of the neural arches on vertebrae (Leitges et al, 2000; Mansouri et al ., 2000; Neidhardt et al, 1997; Schragle et al, 2004).…”

Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression

“…Uncx null mice show abnormal somitogenesis and then develop multiple axial skeletal malformations, including lordosis in the thoracic region, distorted ribs, fused ribs, split ossification center of the vertebral body, and loss of pedicles and transverse process. ( 26 ) The known function of Uncx in the axial skeletal development indicates the involvement of UNCX in the pathomechanism of AIS. In this study, we found that the risk allele of rs78148157 increased the UNCX expression, thus leading to further exploration of its effect of gain of function on the development of the spine.…”