Spatiotemporal MicroRNA-Gene Expression Network Related to Orofacial Clefts

Authors

F Yan
L M Simon
A Suzuki
C Iwaya
P Jia
J Iwata
Z Zhao

Publication Date

10-1-2022

Journal

10.1177/00220345221105816

Abstract

Craniofacial structures change dynamically in morphology during development through the coordinated regulation of various cellular molecules. However, it remains unclear how these complex mechanisms are regulated in a spatiotemporal manner. Here we applied natural cubic splines to model gene and microRNA (miRNA) expression from embryonic day (E) 10.5 to E14.5 in the proximal and distal regions of the maxillary processes to identify spatiotemporal patterns of gene and miRNA expression, followed by constructing corresponding regulatory networks. Three major groups of differentially expressed genes (DEGs) were identified, including 3,927 temporal, 314 spatial, and 494 spatiotemporal DEGs. Unsupervised clustering further resolved these spatiotemporal DEGs into 8 clusters with distinct expression patterns. Interestingly, we found 2 clusters of differentially expressed miRNAs: 1 had 80 miRNAs monotonically decreasing and the other had 97 increasing across developmental stages. To evaluate the phenotypic relevance of these DEGs during craniofacial development, we integrated data from the CleftGeneDB database and constructed the regulatory networks of genes related to orofacial clefts. Our analysis revealed 2 hub miRNAs, mmu-miR-325-3p and mmu-miR-384-5p, that repressed cleft-related genes

Keywords

Animals, Cleft Lip, Cleft Palate, Core Binding Factor Alpha 1 Subunit, Gene Expression, Gene Expression Profiling, Gene Regulatory Networks, Mice, MicroRNAs, cleft lip, developmental biology, gene expression profiling, gene regulatory networks, nonlinear dynamics, spatiotemporal analysis

DOI

10.1177/00220345221105816

PMID

35774010

PMCID

PMC9516630 D

PubMedCentral® Posted Date

6-30-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes