The Transcriptomic Study Of The Regulation Of β-catenin During Murine Kidney Development

The kidneys are vital organs of mammals osmoregulation, and they are the most important excretory organs of human. As well as kidney has the endocrine function, it can generate many important secretions such as renin, erythropoietin, active vitamin D3, prostaglandins, bradykinin, etc. Kidneys also provide the degradation place for parts of the body endocrine hormones and they are renal hormone target organs. These kidney functions can ensure a stable internal environment, so that the metabolism can be carried out normally. It plays an important role for the maintenance of homeostasis of internal environment. The mammalian permanent kidney consists of three cell lineages of different origin:the epithelial cells of the ureter bud, the mesenchymal cells of the nephric blastema and the endothelial cells of the capillaries. Organogenesis is governed by a cascade of morphogenetic interactions between these cell populations, a reciprocal epithelial-mesenchymal interaction between the branching ureter and the metaneph ric mesenchyme, homotypic interactions between cells of the tubular anlagen, stimulation of angiogenesis by the differentiating blastema and a mesenchymal-endothelial interaction guiding the migration of the capillary endothelial cells. While the biology of these interactive events is well known, as described in this overview, the molecular mechanisms are less well mapped out.The molecular basis of embryonic kidney development. The development of the mature mammalian kidney begins with the invasion of metanephric mesenchyme by ureteric bud. Mesenchymal cells near the bud become induced and convert to an epithelium which goes on to generate the functional filtering unit of the kidney, the nephron. The collecting duct system is elaborated by the branching ureter, the growth of which is dependent upon signals from the metanephric mesenchyme. The process of reciprocal induction between ureter and mesenchyme is repeated many times over during development and is the key step in generating the overall architecture of the kidney. Genetic studies in mice have allowed researchers to begin to unravel the molecular signals that govern these early events. These experiments have revealed that a number of essential gene products are required for distinct steps in kidney organogenesis. Although the factors involved are far from completely known a rough framework of a molecular cascade which governs embryonic kidney development is beginning to emerge. We review and summarize the developmental role played by some of these molecules, especially certain transcription factors and growth factors and their receptors.Wnt-P-catenin signaling pathway is one of the most important ways of regulation in embryonic development. It is crucial for the formation and differentiation of multicellular organisms axis, the formation of tissues and organs and updating and differentiation of stem cells. Aberrant activation of the Wnt signaling pathway is involved in the development or lead to a variety of human diseases, such as tumors, neurodegenerative diseases (Alzheimer’s disease) and so on. Researchers detected high expression of β-catenin in the cells of ureter core, stromal cells, and mesenchymal cells of human dysplastic kidney.The exon3 knockout makes fi-catenin over-expression. Several studies had used gene expression profiling of β-catenin over-expression to identify the key genes in this process, but few focused on the involved pathways and co-expression patterns of associated pathways. This article will focus on significant pathways and related transcription factors. Develop the transcriptomic study of the regulation of β-catenin during murine kidney development in depth.First step is collection and collation of microarray data. Microarray technology (Microarray) is a new technology of molecular biology in recent years, it is important for achieving human genome project, exploring the mysteries of the human disease and revealling the nature of life. DNA microarray, also called gene chip, is the product of the rapid development and application of molecular biology and the gradual implementation of the Human Genome Project (Human Geneome Project, HGP). Biologist gain enlightenment and inspiration from the computer chip manufacturing and the wide application of it, melting microelectronics, life sciences, computer science and photoelectrochemical as a whole, it is a new technology and develop from the original nucleic acid hybridization (Northern, Southern). It is one of the main technologies in the third revolution (genome revolution). It is one kind of biochips.The principle of this technique is to integrate a known sequence of gene probes on a solid surface, and a large number of labeled nucleic acid sequences in biological cells or tissues hybridized with that probe arrays. By detecting the position of the corresponding hybridization probes, we can achieve the rapid detection of genetic information. Microarray technology is the core of biotechnology revolution. It has been widely used in medical research. It allow researchers simultaneously monitor the expression levels of thousands of genes.Gene chip produces a large amount of gene expression data. These data provides an important resource for the study of functional genomics. GEO is the largest and completely open high-throughput molecular abundance database, and the main function is to store gene expression data. We retrieve GEO public databases to get the expression profile data which are related to the β-catenin over-expression under exon3 knockout. The database is a flexible and open design that allows users or researchers to present, preserve and retrieve many different types of data. Login GEO public database at:https://www.ncbi.nlm.nih.gov/geo/.Then we need GSEA analysis the data to get valuable information. How to tap the useful information from massive gene expression information and how to carry out biological professional interpretation, they are important challenges in the field of gene expression data analysis. We can use gene enrichment analysis method. There are many gene enrichment analysis methods, commonly used gene enrichment analysis method can be summarized into two categories, namely bottom-up and top-down method. This study used gene enrichment analysis method from the bottom-up, and it is called GSEA. Gene set enrichment can analysis the expression data collaborative difference at the level of gene set to determine the specific pathway.Microarray gene expression data will be sorted first, then they were compared with a pre-built set of functional genes to find whether these genes detected by microarray hybridization will be appeared in the selected functional gene sets. And it will find the ranking position of the genes detected by microarray hybridization throughout gene expression data. Analysis of these genes occurs in a particular function of genes whether have a common trend of expression. That is the nature of the enrichment. GSEA concerns not the expression a few genes that altered significantly, but the expression consistency of the entire hybrid data in a particular functional genes. In order to interpret the biological information contained in the data.Here, we used a microarray data set from the public database library of GEO (Gene Expression Omnibus), which was associated with renal transcriptome in the mous e model of β-catenin over-expression. To be more powerful than conventional single-gene methods in the study of renal development, we performed gene set enrichment analysis (GSEA) on the data sets and applied candidate transcription factors selection. GSEA is whole genome microarray data analysis tools, and you can use free after download. We functional annotate these significant pathways by KEGG Kyoto encyclopedia of genes and genomes, also called KEGG is a database which can systematically analyze gene function and genome information. It integrates information on genomics, biochemistry and system functional genomics to help researchers study genes and gene expression information as a whole.As a result,63 up-regulated pathways such as Notch signaling pathway and mTOR signaling pathway and 43 down-regulated pathways such as ABC transporters and Type I diabetes mellitus were identified as β-catenin over-expression target pathways in exon3 of fi-catenin knockout mouse kidney and most of them had not been reported on previously. After KEGG functional annotation, these significant pathways were eventually divided into six functional categories. They are cellular processes functional category, environmental information processing category, genetic information processing category, human disease category, metabolism category, and organismal systems category.We analysis on a few transcription factors which has significant correlation in important representative pathways such as PAX2, SREBP1 and PPAR_DR1. Furthermore we analysis on the important relevant pathways such as mTOR pathways and JAK-STAT pathways. Finally, co-expression networks of related pathways were constructed with the significant core genes and transcription factors such as STATs and PAXs. The results of our study may help us better understand the regulation ofβ-catenin in renal development in mice kidney in genome-wild.