Spatial Multi-omics Reveals the Role of the Wnt Modulator, Dkk2, in Palatogenesis

Multiple genetic and environmental etiologies contribute to the pathogenesis of cleft palate, which is the most common of the inherited disorders of the craniofacial complex. Insights into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesi...

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Bibliographic Details
Published in:	Journal of dental research p. 220345241256600
Main Authors:	Piña, J O, Raju, R, Roth, D M, Winchester, E W, Padilla, C, Iben, J, Faucz, F R, Cotney, J L, D'Souza, R N
Format:	Journal Article
Language:	English
Published:	United States 23-06-2024
Subjects:	craniofacial biology/genetics single-cell sequencing cleft palate craniofacial anomalies signal transduction gene expression
Online Access:	Get full text
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Summary:	Multiple genetic and environmental etiologies contribute to the pathogenesis of cleft palate, which is the most common of the inherited disorders of the craniofacial complex. Insights into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesis are limited and needed for the development of innovative diagnostics and cures. This study used the mouse model with a consistent phenotype of cleft secondary palate to investigate the role of in the process of palatal osteogenesis. Although prior research has identified the upregulation of Wnt pathway modulators and in palate mesenchyme, limitations of spatial resolution and technology restricted a more robust analysis. Here, data from single-nucleus transcriptomics and chromatin accessibility assays validated by in situ highly multiplex targeted single-cell spatial profiling technology suggest a distinct relationship between and osteogenic populations. Loss of results in spatially restricted osteogenic domains bounded by , which normally interfaces with in the mesenchyme. Moreover, the loss of leads to a disruption in the normal osteodifferentiaion of palatal osteogenic mesenchymal cells. These results suggest that Pax9-dependent Wnt signaling modulators influence osteogenic programming during palate formation, potentially contributing to the observed cleft palate phenotype.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-0345 1544-0591 1544-0591
DOI:	10.1177/00220345241256600