Influence of Hoxd11 on Wnt4 and Wnt7b expression patterns during metatarsal development

Location

Philadelphia, PA

Start Date

17-4-2026 1:30 PM

End Date

17-4-2026 2:30 PM

Description

INTRODUCTION: The Wnt signaling pathway is highly conserved and essential for embryonic development via regulation of cell migration, differentiation, and overall homeostasis. Hox genes, including Hoxd11, are one of many factors involved in Wnt signaling pathways. Hox genes are also influential in limb morphogenesis. Posterior Hox genes (genes 9-13) have been shown to down-regulate Wnt receptors and decrease signaling activity, thus allowing for slowed elongation of the axial skeleton. We have identified several differentially expressed Wnt pathway genes, including Wnt4 and Wnt7b, in mRNA sequencing data comparing embryonic limbs of wild type and homozygous Hoxd11 loss-of-function mice.

OBJECTIVE: Our study investigates the role Hoxd11 plays on Wnt4 and Wnt7b expression in bone and growth plate cartilage of the metatarsal and distal tibia.

METHODS: We performed RNAscope™ (ACD Bio) in situ hybridization assays on tissue sections from postnatal day 0 wild type and homozygous Hoxd11 loss-of-function mouse hind limbs to determine mRNA expression patterns of Wnt4 and Wnt7b.

RESULTS: Our results indicate that homozygous Hoxd11 loss-of-function mouse limbs display stronger expression of Wnt4 in the perichondrium and columnar zone of metatarsal growth plates compared to wild type specimens. We observe slightly decreased expression of Wnt7b in the perichondrium of homozygous Hoxd11 loss-of-function specimens compared to wild type.

CONCLUSION: The increased expression of Wnt4 seen in Hoxd11 homozygous loss-of-function specimens indicates that, without functional Hoxd11 present, at least some Wnt is upregulated in and around developing bone and growth plate cartilage. Wnt7b expression is more confined to perichondrium around the groove of Ranvier for the growth plate. Hoxd11 appears to interact with multiple Wnt genes in the developing metatarsal. These results may indicate premature terminal differentiation and impaired maturation of chondrocytes within growth plate regions of metatarsals, inferring Hoxd11 is an essential regulator of proper bone growth and development.

Embargo Period

5-20-2026

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Apr 17th, 1:30 PM Apr 17th, 2:30 PM

Influence of Hoxd11 on Wnt4 and Wnt7b expression patterns during metatarsal development

Philadelphia, PA

INTRODUCTION: The Wnt signaling pathway is highly conserved and essential for embryonic development via regulation of cell migration, differentiation, and overall homeostasis. Hox genes, including Hoxd11, are one of many factors involved in Wnt signaling pathways. Hox genes are also influential in limb morphogenesis. Posterior Hox genes (genes 9-13) have been shown to down-regulate Wnt receptors and decrease signaling activity, thus allowing for slowed elongation of the axial skeleton. We have identified several differentially expressed Wnt pathway genes, including Wnt4 and Wnt7b, in mRNA sequencing data comparing embryonic limbs of wild type and homozygous Hoxd11 loss-of-function mice.

OBJECTIVE: Our study investigates the role Hoxd11 plays on Wnt4 and Wnt7b expression in bone and growth plate cartilage of the metatarsal and distal tibia.

METHODS: We performed RNAscope™ (ACD Bio) in situ hybridization assays on tissue sections from postnatal day 0 wild type and homozygous Hoxd11 loss-of-function mouse hind limbs to determine mRNA expression patterns of Wnt4 and Wnt7b.

RESULTS: Our results indicate that homozygous Hoxd11 loss-of-function mouse limbs display stronger expression of Wnt4 in the perichondrium and columnar zone of metatarsal growth plates compared to wild type specimens. We observe slightly decreased expression of Wnt7b in the perichondrium of homozygous Hoxd11 loss-of-function specimens compared to wild type.

CONCLUSION: The increased expression of Wnt4 seen in Hoxd11 homozygous loss-of-function specimens indicates that, without functional Hoxd11 present, at least some Wnt is upregulated in and around developing bone and growth plate cartilage. Wnt7b expression is more confined to perichondrium around the groove of Ranvier for the growth plate. Hoxd11 appears to interact with multiple Wnt genes in the developing metatarsal. These results may indicate premature terminal differentiation and impaired maturation of chondrocytes within growth plate regions of metatarsals, inferring Hoxd11 is an essential regulator of proper bone growth and development.