Abstract
Normal mammalian palatogenesis is a complex process that requires the occurrence of a tightly regulated series of specific and sequentially regulated cellular events. Cleft lip/palate (CLP), the most frequent craniofacial malformation birth defects, may occur if any of these events undergo abnormal interference. Such defects not only affect the patients, but also pose a financial risk for the families. In our recent study, the miniature pig was shown to be a valuable alternative large animal model for exploring human palate development by histology. However, few reports exist in the literature to document gene expression and function during swine palatogenesis. To better understand the genetic regulation of palate development, an mRNA expression profiling analysis was performed on miniature pigs, Sus scrofa. Five key developmental stages of miniature pigs from embryonic days (E) 30–50 were selected for transcriptome sequencing. Gene expression profiles in different palate development stages of miniature pigs were identified. Nine hundred twenty significant differentially expressed genes were identified, and the functional characteristics of these genes were determined by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Some of these genes were associated with HH (hedgehog), WNT (wingless-type mouse mammary tumor virus integration site family), and MAPK (mitogen-activated protein kinase) signaling, etc., which were shown in the literature to affect palate development, while some genes, such as HIP (hedgehog interacting protein), WNT16, MAPK10, and LAMC2 (laminin subunit gamma 2), were additions to the current understanding of palate development. The present study provided a comprehensive analysis for understanding the dynamic gene regulation during palate development and provided potential ideas and resources to further study normal palate development and the etiology of cleft palate.
Highlights
The most frequent birth defects causing craniofacial abnormalities are congenital cleft lip/palate (CLP)
Analysis of mRNA Sequencing in Different Stages of Sus scrofa Secondary Palate Development 2.1
Since the primary palate has a distinct developmental origin from the secondary palate, and the development of the secondary palate serves as a paradigm for embryonic development in general, as virtually all of the molecular processes and signaling pathways associated with normal palatal ontogeny are mirrored in the embryogenesis of multiple other systems, the palatogenesis is focus on the secondary palate [1,2,17,18,34]
Summary
The most frequent birth defects causing craniofacial abnormalities are congenital cleft lip/palate (CLP). The majority of CLP (70%) are regarded as nonsyndromic, with the clefts occurring without other anomalies. Children are affected by considerable morbidity, families are burdened with substantial financial risk, and a concomitant social burden may be caused by CLP. Patients with CLP may experience problems with feeding, speaking, and hearing and undergo subsequent treatment from surgery, dental treatment, and speech training to psychosocial intervention [1,2,3]. As CLP is considered a complex etiology with both genetic and environmental factors, occurs in the early stage of development, and has modest recurrence rates, specific etiologic factors are difficult to identify. Deeper insights into the pathogenesis of CLP may be explored by an integration of candidate genes and genome-wide studies and analyses of epidemiologic and animal models
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