Transcriptome analysis of coding and long non-coding RNAs highlights the regulatory network of cascade initiation of permanent molars in miniature pigs

Fu Wang,Jinsong Wang,Songlin Wang,Wei Cong,Jie Du,Zhipeng Fan,Xiaoshan Wu,Chunmei Zhang,Min Yang,Yang Li

doi:10.1186/s12864-017-3546-4

Fu Wang, Jinsong Wang + Show 8 more

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https://doi.org/10.1186/s12864-017-3546-4

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Abstract

BackgroundIn diphyodont mammals, the additional molars (permanent molars) bud off from the posterior-free end of the primary dental lamina compared with successional teeth (replacement teeth) budding off from the secondary dental lamina. The diphyodont miniature pig has proved to be a valuable model for studying human molar morphogenesis. The additional molars show a sequential initiation pattern related to the specific tooth development stage of additional molars in miniature pigs during the morphogenesis of additional molars. However, the molecular mechanisms of the regulatory network of mRNAs and long non-coding RNAs during sequential formation of additional molars remain poorly characterized in diphyodont mammals. Here, we performed RNA-seq and microarray on miniature pigs at three key molar developmental stages to examine their differential gene expression profiles and potential regulatory networks during additional molar morphogenesis.ResultsWe have profiled the differential transcript expression and functional networks during morphogenesis of additional molars in miniature pigs. We also have identified the coding and long non-coding transcripts using Coding-Non-Coding Index (CNCI) and annotated transcripts through mapping to the porcine, Wuzhishan miniature pig, mice, cow and human genomes. Many new unannotated genes plus 450 putative long intergenic non-coding RNAs (lincRNAs) were identified. Detailed regulatory network analyses reveal that WNT and TGF-β pathways are critical in regulating sequential morphogenesis of additional molars.ConclusionsThis is the first study to comprehensively analyze the spatiotemporal dynamics of coding and long non-coding transcripts during morphogenesis of additional molars in diphyodont mammals. The miniature pig serves as a large model animal to elucidate the relationship between morphogenesis and transcript level during the cascade initiation of additional molars. Our data provide fundamental knowledge and a basis for understanding the molecular mechanisms governing cascade initiation of additional molars, but also provide an important resource for developmental biology research.

Highlights

In diphyodont mammals, the additional molars bud off from the posterior-free end of the primary dental lamina compared with successional teeth budding off from the secondary dental lamina
Developmental patterns of additional molars Our previous study showed that mandibular additional molar morphogenesis in miniature pigs initiates from the distal extension of the primary dental lamina developing posterior to the third deciduous molar, which differed from replacement teeth derived from secondary dental lamina [2]
We further identified an interesting sequential initiation pattern of additional molars in the mandible ramus related to spatiotemporal morphogenesis, where Second mola (M2) initiated from the posterior-free end of the dental lamina over the First molar (M1) at E60 when the M1 progressed to the late bell stage

Summary

Introduction

The additional molars (permanent molars) bud off from the posterior-free end of the primary dental lamina compared with successional teeth (replacement teeth) budding off from the secondary dental lamina. The molecular mechanisms of the regulatory network of mRNAs and long non-coding RNAs during sequential formation of additional molars remain poorly characterized in diphyodont mammals. We performed RNA-seq and microarray on miniature pigs at three key molar developmental stages to examine their differential gene expression profiles and potential regulatory networks during additional molar morphogenesis. The successional teeth arise from the extension of the dental lamina on the lingual aspect of the deciduous teeth, and additional molars bud off from the posterior extension of the dental lamina. The process of additional molars from initiation to final eruption in humans takes a long time, from 6 (without the third molar) to 12 (with the third molar) years in different individuals

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