The Role of Hoxa11 and Hoxd11 Expression Patterns in Determining Calcaneus Shape in Mice
Location
Philadelphia, PA
Start Date
30-4-2025 1:00 PM
End Date
30-4-2025 4:00 PM
Description
INTRODUCTION: Hox genes play a vital role in skeletal development in the embryo and continue to function in the maintenance and repair of bone throughout life. In embryonic development, Hoxa11 and Hoxd11 genes are expressed near the developing ankle, specifically the calcaneus. Previous studies demonstrate that mice with various combinations of Hoxa11 and Hoxd11 loss-of-function mutations exhibit statistically significant calcaneus shape differences compared to the wild-type. However, the detailed expression patterns of these two genes have not been thoroughly characterized in the calcaneus and surrounding tissues.
OBJECTIVES: The present study aims to compare the expression patterns of Hoxa11 and Hoxd11 in and around the developing calcaneus. We compared the regions of gene expression in wild-type mice to known shape differences that were identified in previous studies in calcanei of mice with Hoxa11 and Hoxd11 loss-of-function mutations.
METHODS: We conducted RNAscope™ in situ hybridization to localize Hoxa11 and Hoxd11 mRNA expression in histological sections of wild-type mouse hind paws at postnatal days (P)0, P4, P9. Histological slides were scanned using a Motic slide scanner, and Motic imaging software was used to compare Hoxa11 and Hoxd11 gene expression in and around the calcaneus.
RESULTS: Hoxa11 expression is strong throughout the calcaneus and surrounding tissue, including in the perichondrium and chondrocytes. Several anatomical locations exhibit increased staining intensity, including the perichondrium of the calcaneal tuberosity and regions of the sustentaculum tali. Hoxd11 expression was minimal in and around the calcaneus; however, expression was observed in the calcaneal tendon, and near the site of insertion into the calcaneal tuberosity. These expression patterns correspond to shape changes observed in previous studies of mice with Hoxa11 and Hoxd11 loss-of-function mutations, whereby knocking out Hoxa11 resulted in shortened calcaneal tuberosity and reduced size of the sustentaculum tali.
Conclusion: The widespread Hoxa11 expression seen in wild-type mice identifies Hoxa11 as a substantial contributor to calcaneus development. The overlap of morphological changes in Hoxa11 knockout mice with the distribution of Hoxa11 gene expression in the wild-type calcaneus further supports the role of Hoxa11. Moreover, these data suggest a reduced role of Hoxd11 in determining calcaneus shape and morphology, although further investigation is needed to assess the interaction between these two genes. Understanding the differential expression of Hoxa11 and Hoxd11 in the calcaneus may provide insight into their distinct functions in bone formation and development.
Embargo Period
5-20-2025
The Role of Hoxa11 and Hoxd11 Expression Patterns in Determining Calcaneus Shape in Mice
Philadelphia, PA
INTRODUCTION: Hox genes play a vital role in skeletal development in the embryo and continue to function in the maintenance and repair of bone throughout life. In embryonic development, Hoxa11 and Hoxd11 genes are expressed near the developing ankle, specifically the calcaneus. Previous studies demonstrate that mice with various combinations of Hoxa11 and Hoxd11 loss-of-function mutations exhibit statistically significant calcaneus shape differences compared to the wild-type. However, the detailed expression patterns of these two genes have not been thoroughly characterized in the calcaneus and surrounding tissues.
OBJECTIVES: The present study aims to compare the expression patterns of Hoxa11 and Hoxd11 in and around the developing calcaneus. We compared the regions of gene expression in wild-type mice to known shape differences that were identified in previous studies in calcanei of mice with Hoxa11 and Hoxd11 loss-of-function mutations.
METHODS: We conducted RNAscope™ in situ hybridization to localize Hoxa11 and Hoxd11 mRNA expression in histological sections of wild-type mouse hind paws at postnatal days (P)0, P4, P9. Histological slides were scanned using a Motic slide scanner, and Motic imaging software was used to compare Hoxa11 and Hoxd11 gene expression in and around the calcaneus.
RESULTS: Hoxa11 expression is strong throughout the calcaneus and surrounding tissue, including in the perichondrium and chondrocytes. Several anatomical locations exhibit increased staining intensity, including the perichondrium of the calcaneal tuberosity and regions of the sustentaculum tali. Hoxd11 expression was minimal in and around the calcaneus; however, expression was observed in the calcaneal tendon, and near the site of insertion into the calcaneal tuberosity. These expression patterns correspond to shape changes observed in previous studies of mice with Hoxa11 and Hoxd11 loss-of-function mutations, whereby knocking out Hoxa11 resulted in shortened calcaneal tuberosity and reduced size of the sustentaculum tali.
Conclusion: The widespread Hoxa11 expression seen in wild-type mice identifies Hoxa11 as a substantial contributor to calcaneus development. The overlap of morphological changes in Hoxa11 knockout mice with the distribution of Hoxa11 gene expression in the wild-type calcaneus further supports the role of Hoxa11. Moreover, these data suggest a reduced role of Hoxd11 in determining calcaneus shape and morphology, although further investigation is needed to assess the interaction between these two genes. Understanding the differential expression of Hoxa11 and Hoxd11 in the calcaneus may provide insight into their distinct functions in bone formation and development.
Comments
Awarded "Camille DiLullo Award for Excellence in Research" at PCOM Research Day 2025