Potential regulatory interactions between Hoxd11 and Wnt signaling pathways during limb skeletal development
Location
Philadelphia, PA
Start Date
17-4-2026 1:30 PM
End Date
17-4-2026 2:30 PM
Description
INTRODUCTION: 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 Hox11 genes are known to be expressed in and around the developing hand and foot. While Hox11 genes are associated with morphological changes in the hand and foot, including wrist and ankle bones, little is known about their role in transcriptional regulation of other developmental genes. The present study uses mRNA sequencing to identify differentially expressed genes between the developing autopod of wild type mice and mice with Hoxd11 loss-of-function mutations.
OBJECTIVE: This study seeks to identify gene expression changes related to skeletal development in the embryonic mouse foot when Hoxd11 function is lost.
METHODS: We performed mRNA sequencing on embryonic 14.5 day mouse autopods with and without Hoxd11 loss-of-function mutations. Differentially expressed genes (DEGs) were then identified between genotypes. Genes with p-value < 0.05 and |log2 fold change| >1 were considered differentially expressed. DEGs were assessed for their biological relevance with normalized and raw count data. Several genes were selected for visualization using RNAscope™ in situ hybridization in postnatal day (P)0 neonatal mice to determine whether or not they are expressed in developing bone, cartilage, or perichondrium.
RESULTS: Several genes involved in Wnt signaling pathways were identified with a large log2 fold change and low adjusted p-value between wild type and both Hoxd11+/- and Hoxd11-/- genotypes. This includes many Wnt ligands and receptors. Some of these genes, including Wnt7b and Ror2, have also been identified as differentially expressed between growth plate-forming and non-forming ends of metatarsals in wild type mice. Wnt7b, Wnt4, Ror2, and Lrp5 were selected for preliminary investigation with in situ hybridization. All demonstrate staining in and around developing bone and cartilage at P0 and therefore warrant further investigation.
CONCLUSION: RNA-seq results support a role for Hoxd11 regulation of Wnt pathways, due to a large number of Wnt ligands and pathway proteins that are significantly differentially expressed. Three Wnt signaling pathways have been described: canonical, planar cell polarity, and calcium pathway. Previous studies have shown Wnt4 to be involved in canonical and non-canonical signaling depending on the biological context, and it is unclear in which pathway it may be acting during limb development and skeletal growth. Posterior Hox genes (genes 9-13) have also been shown to down-regulate Wnt receptors and decrease signaling activity, thus allowing for slowed elongation of the axial skeleton. Future studies will work to better understand the interaction between Hox and Wnt pathways in skeletal development.
Embargo Period
5-19-2026
Potential regulatory interactions between Hoxd11 and Wnt signaling pathways during limb skeletal development
Philadelphia, PA
INTRODUCTION: 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 Hox11 genes are known to be expressed in and around the developing hand and foot. While Hox11 genes are associated with morphological changes in the hand and foot, including wrist and ankle bones, little is known about their role in transcriptional regulation of other developmental genes. The present study uses mRNA sequencing to identify differentially expressed genes between the developing autopod of wild type mice and mice with Hoxd11 loss-of-function mutations.
OBJECTIVE: This study seeks to identify gene expression changes related to skeletal development in the embryonic mouse foot when Hoxd11 function is lost.
METHODS: We performed mRNA sequencing on embryonic 14.5 day mouse autopods with and without Hoxd11 loss-of-function mutations. Differentially expressed genes (DEGs) were then identified between genotypes. Genes with p-value < 0.05 and |log2 fold change| >1 were considered differentially expressed. DEGs were assessed for their biological relevance with normalized and raw count data. Several genes were selected for visualization using RNAscope™ in situ hybridization in postnatal day (P)0 neonatal mice to determine whether or not they are expressed in developing bone, cartilage, or perichondrium.
RESULTS: Several genes involved in Wnt signaling pathways were identified with a large log2 fold change and low adjusted p-value between wild type and both Hoxd11+/- and Hoxd11-/- genotypes. This includes many Wnt ligands and receptors. Some of these genes, including Wnt7b and Ror2, have also been identified as differentially expressed between growth plate-forming and non-forming ends of metatarsals in wild type mice. Wnt7b, Wnt4, Ror2, and Lrp5 were selected for preliminary investigation with in situ hybridization. All demonstrate staining in and around developing bone and cartilage at P0 and therefore warrant further investigation.
CONCLUSION: RNA-seq results support a role for Hoxd11 regulation of Wnt pathways, due to a large number of Wnt ligands and pathway proteins that are significantly differentially expressed. Three Wnt signaling pathways have been described: canonical, planar cell polarity, and calcium pathway. Previous studies have shown Wnt4 to be involved in canonical and non-canonical signaling depending on the biological context, and it is unclear in which pathway it may be acting during limb development and skeletal growth. Posterior Hox genes (genes 9-13) have also been shown to down-regulate Wnt receptors and decrease signaling activity, thus allowing for slowed elongation of the axial skeleton. Future studies will work to better understand the interaction between Hox and Wnt pathways in skeletal development.