Functional Studies Of Dip2b Gene In Lung Development

Dip2b gene is a member of Disco-interacting protein 2(Dip2)gene family,encoding proteins that are highly conserved in vertebrates and invertebrates.High-throughput sequencing technology was used in current researches on Dip2 b to analyze its potential roles as a target gene in association with diseases.However,the primary biological function of Dip2 b itself has not been reported.According to our previous work,Dip2 b knockout mice showed poor activity,respiratory stress and postnatal death.Although the mechanism remains unclear,it is suggested that Dip2 b has important biological functions.Since birth defects were often associated with diseases with abnormal heart or lung development and function,we investigated the role of Dip2 b gene in lung development first.Histological observation using Dip2 b knockout mouse model with LacZ-NEO reporter gene showed that Dip2 b was expressed in the trachea,bronchus and alveoli,and results of frozen section lacZ staining showed that Dip2 b was mainly expressed in the lung parenchymal structure,such as the epithelium of trachea and alveoli,but not in the lung mesenchymal tissue.Dip2 b knockout led to structural and functional abnormalities in mice.Structurally,the number of alveoli decreased,with overdeveloped mesenchymal tissue,thickened septum and decreased number of respiratory bronchioles.Functionally,the newborns showed poor activity,respiratory stress,abnormal skin color and died within 24 hours after birth.To further investigate genes and pathways regulated by Dip2 b gene in lung development,wild type and Dip2 b knockout mice were subjected for RNA sequencing.The results showed multiple biological processes related to lung development were affected.The KEGG enrichment showed that Dip2 b participated in Hedgehog signaling pathway and regulated lung and embryo development with growth factors such as SHH,WNT5 A.Finally,a lung specific expression transgenic mouse model was constructed by using the conditional knockout system to investigate the regulatory effect of lung Dip2 b expression on embryonic development.In conclusion,this study suggested,at least in part,of the biological function of Dip2 b in lung development,providing a base for further analyzing the physiological and pathological significance of Dip2 b gene and Dip2 gene family.