SHOT, a SHOX-related homeobox gene, is implicated in craniofacial, brain, heart, and limb development

Abstract

Deletion of the SHOX region on the human sex chromosomes has been shown to result in idiopathic short stature and proposed to play a role in the short stature associated with Turner syndrome. We have identified a human paired-related homeobox gene, SHOT, by virtue of its homology to the human SHOX and mouse OG-12 genes. Two different isoforms were isolated, SHOTa and SHOTb, which have identical homeodomains and share a C-terminal 14-amino acid residue motif characteristic for craniofacially expressed homeodomain proteins. Differences between SHOTa and b reside within the N termini and an alternatively spliced exon in the C termini. In situ hybridization of the mouse equivalent, OG-12, on sections from staged mouse embryos detected highly restricted transcripts in the developing sinus venosus (aorta), female genitalia, diencephalon, mes-and myelencephalon, nasal capsula, palate, eyelid, and in the limbs. SHOT was mapped to human chromosome 3q25-q26 and OG-12 within a syntenic region on chromosome 3. Based on the localization and expression pattern of its mouse homologue during embryonic development, SHOT represents a candidate for the Cornelia de Lange syndrome.

Expression survey of genes critical for tooth development in the human embryonic tooth germ

“…4D). The similar situation was also observed for the expression of SHOX2, a member of the short stature homeobox gene family (Blaschke et al, 1998;Semina et al, 1998). In the developing mouse tooth, Shox2 expression is restricted to the dental epithelium from the early bud stage to the cap stage ( Fig.…”

Gene expression analysis reveals that formation of the mouse anterior secondary palate involves recruitment of cells from the posterior side

“…In mouse, only one Shox family member, Shox-2, has been identified to date Cobb et al, 2006). The amino acid sequences between human and mouse Shox-2 proteins are 99% identical (Blaschke et al, 1998;Semina et al, 1998). Unlike SHOX, the association of SHOX-2 gene with human disease has not been reported.…”

“…The founding member of this family, human SHOX gene, is associated with bone related short-stature disorders including Turner syndrome and Leri-Weill syndromes (Clement-Jones et al, 2000). Human SHOX2 gene shares 80% similarity with human SHOX gene at amino acid level in the homeodomain and C-terminal regions (Blaschke et al, 1998;Semina et al, 1998). In mouse, only one Shox family member, Shox-2, has been identified to date Cobb et al, 2006).…”

“…Mouse Shox-2 gene belongs to a recently identified paired-related homeobox gene family that also found in humans and chicken (Blaschke et al, 1998;Semina et al, 1998;Clement-Jones et al, 2000;Cobb et al, 2006;Tiecke et al, 2006). The founding member of this family, human SHOX gene, is associated with bone related short-stature disorders including Turner syndrome and Leri-Weill syndromes (Clement-Jones et al, 2000).…”

Predictability of Hand Skill and Cognitive Abilities From Craniofacial Width in Right- And Left-Handed Men and Women: Relation of Skeletal Structure to Cerebral Function

“…Accordingly, there are genes exhibiting multiple functions at different stages of development or in different tissues and cell types. Blaschke et al (1998) have identified a human paired-related homeobox gene, SHOT, which is implicated in craniofacial, brain, heart, and limb development. Merlo et al (2000) have reported that DIx genes, comprising a highly conserved family of homeobox genes, are expressed in spatially and temporally restricted patterns in craniofacial primordia, basala telencephalon, and diencephalon, and in distal regions of extending appendages, including the limb and the genital bud; these genes seem to have multiple functions at different stages of development or in different tissues and cell types.…”