Hox patterning of the vertebrate rib cage

Abstract

Unlike the rest of the axial skeleton, which develops solely from somitic mesoderm, patterning of the rib cage is complicated by its derivation from two distinct tissues. The thoracic skeleton is derived from both somitic mesoderm, which forms the vertebral bodies and ribs, and from lateral plate mesoderm, which forms the sternum. By generating mouse mutants in Hox5, Hox6 and Hox9 paralogous group genes, along with a dissection of the Hox10 and Hox11 group mutants, several important conclusions regarding the nature of the 'Hox code' in rib cage and axial skeleton development are revealed. First, axial patterning is consistently coded by the unique and redundant functions of Hox paralogous groups throughout the axial skeleton. Loss of paralogous function leads to anterior homeotic transformations of colinear regions throughout the somite-derived axial skeleton. In the thoracic region, Hox genes pattern the lateral plate-derived sternum in a non-colinear manner, independent from the patterning of the somite-derived vertebrae and vertebral ribs. Finally, between adjacent sets of paralogous mutants, the regions of vertebral phenotypes overlap considerably; however, each paralogous group imparts unique morphologies within these regions. In all cases examined, the nextmost posterior Hox paralogous group does not prevent the function of the more-anterior Hox group in axial patterning. Thus, the 'Hox code' in somitic mesoderm is the result of the distinct, graded effects of two or more Hox paralogous groups functioning in any anteroposterior location.

CTCF-mediated topological boundaries during development foster appropriate gene regulation

“…Nested Hox expression patterns the mesoderm-derived axial skeleton along the rostro-caudal axis (Garcia-Gasca and Spyropoulos 2000; McIntyre et al 2007). Thus, we tested the CTCF-demarcated TAD boundaries within the HoxA and HoxC clusters for their input into skeletal patterning during embryonic development.…”

Three-dimensional morphometrics of thoracic vertebrae in Neandertals and the fossil evidence from El Sidrón (Asturias, Northern Spain)

“…This could reflect developmental effects between thoracic and adjacent cervical segments (McIntyre et al, 2007), because in Neandertals cervical vertebrae have been shown recently to be "mediolaterally wider and dorsoventally longer" (Gómez-Olivencia et al, 2013b:608). Such differences should translate into greater overall centroid sizes of Neandertal vertebrae in the cervico-thoracic transition, although cervical vertebrae still need to be investigated with 3D-GM.…”

“…Thus, we propose that difference in transverse process orientation between Neandertals and the modern human reference sample likely reflects true species differences. These species-specific differences may have a serial developmental genetic signal in more cranial levels T3-T5 (McIntyre et al, 2007), and may involve features less related to seriality in central-lower parts of the thoracic spine. Although more research is necessary in this respect, differences in transverse process orientation may add to the reduced vertebral body heights shown already in other studies Been et al, 2017a).…”

HOX transcription factors are potential therapeutic targets in non-small-cell lung cancer (targeting HOX genes in lung cancer)

“…The HOX genes are also divided into paralogue groups -genes that have the equivalent position in each cluster (1 -13) -thus HOXA1, for example, is the 3 0 most gene in cluster A (Scott, 1993). Whereas some HOX genes have distinct functions in specific contexts, many others have overlapping or redundant functions, both during early development (McIntyre et al, 2007) and in malignant cells (Eklund, 2007). This redundancy in HOX function is based in part upon the binding of similar DNA sequences and also on the interaction of HOX proteins with a common set of co-factors including PBX and MEIS.…”