The role of Hoxa11 and Hoxd11 in calcaneus shape determination
Location
Philadelphia, PA
Start Date
17-4-2026 1:30 PM
End Date
17-4-2026 2:30 PM
Description
NTRODUCTION: Hox genes are an important family of developmental patterning genes that play a key role in embryonic skeletal development. They pattern skeletal morphology throughout the body, and Hoxa11 and Hoxd11 are known to be expressed in and around the developing ankle. The calcaneus fails to form in mice with both Hoxa11 and Hoxd11 knocked out, but less is known about morphological changes in mice with at least one functional allele for either of these genes. We have previously observed variation in calcaneus length in mice with Hox11 loss-of-function mutations. The present study investigates adult mouse calcaneus morphology when three or fewer Hoxa11 and Hoxd11 loss-of-function alleles are present.
METHODS: This project evaluates the adult morphology in calcanei of wild-type mice and mice with one, two, and three Hoxa11 and Hoxd11 loss-of-function alleles. Adult mouse limbs were scanned using micro-computed tomography (micro-CT) imaging at 5um resolution on a GE v|tome|x L 300. Scans were processed and visualized using Dragonfly ORS software. 3D geometric morphometric analysis was performed using auto3Dgm using surface semi-landmarks on scaled and aligned specimens (n=66). Shape differences were determined using Principal Components (PC) analysis. We chose 11 linear measurements, based on the PCs generated with auto3dgm, to determine differences between calcaneal dimensions between genotypes. Linear measurements were obtained for each bone using 3D Slicer. Measurements were compared across genotypes to evaluate potential morphological differences associated with genetic variation.
RESULTS: Analysis indicates measurable variation across several calcaneal dimensions, with statistically significant differences observed between Hox11 genotypes. Greater differences are observed between genotypes with Hoxa11 loss-of-function mutations than those with Hoxd11 loss-of-function mutations for several of the linear measurements, particularly those involving overall calcaneal length and sustentaculum tali morphology. Distal calcaneal width and peroneal tubercle length did not show significant differences.
CONCLUSIONS: These results suggest that calcaneus shape is more susceptible to changes in Hoxa11 expression than Hoxd11 expression. While Hox genes are known to play an important role in developmental patterning of the skeleton, these results further demonstrate that these genes can differentially impact the shapes of specific skeletal structures.
Embargo Period
5-20-2026
The role of Hoxa11 and Hoxd11 in calcaneus shape determination
Philadelphia, PA
NTRODUCTION: Hox genes are an important family of developmental patterning genes that play a key role in embryonic skeletal development. They pattern skeletal morphology throughout the body, and Hoxa11 and Hoxd11 are known to be expressed in and around the developing ankle. The calcaneus fails to form in mice with both Hoxa11 and Hoxd11 knocked out, but less is known about morphological changes in mice with at least one functional allele for either of these genes. We have previously observed variation in calcaneus length in mice with Hox11 loss-of-function mutations. The present study investigates adult mouse calcaneus morphology when three or fewer Hoxa11 and Hoxd11 loss-of-function alleles are present.
METHODS: This project evaluates the adult morphology in calcanei of wild-type mice and mice with one, two, and three Hoxa11 and Hoxd11 loss-of-function alleles. Adult mouse limbs were scanned using micro-computed tomography (micro-CT) imaging at 5um resolution on a GE v|tome|x L 300. Scans were processed and visualized using Dragonfly ORS software. 3D geometric morphometric analysis was performed using auto3Dgm using surface semi-landmarks on scaled and aligned specimens (n=66). Shape differences were determined using Principal Components (PC) analysis. We chose 11 linear measurements, based on the PCs generated with auto3dgm, to determine differences between calcaneal dimensions between genotypes. Linear measurements were obtained for each bone using 3D Slicer. Measurements were compared across genotypes to evaluate potential morphological differences associated with genetic variation.
RESULTS: Analysis indicates measurable variation across several calcaneal dimensions, with statistically significant differences observed between Hox11 genotypes. Greater differences are observed between genotypes with Hoxa11 loss-of-function mutations than those with Hoxd11 loss-of-function mutations for several of the linear measurements, particularly those involving overall calcaneal length and sustentaculum tali morphology. Distal calcaneal width and peroneal tubercle length did not show significant differences.
CONCLUSIONS: These results suggest that calcaneus shape is more susceptible to changes in Hoxa11 expression than Hoxd11 expression. While Hox genes are known to play an important role in developmental patterning of the skeleton, these results further demonstrate that these genes can differentially impact the shapes of specific skeletal structures.