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Series GSE45568 Query DataSets for GSE45568
Status Public on Mar 29, 2013
Title Systematic analysis of palatal transcriptome to identify cleft palate genes within TGFbeta3-knockout mice alleles: RNA-Seq analysis of TGFbeta3 Mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Background: In humans, cleft palate (CP) accounts for one of the largest number of birth defects with a complex genetic and environmental etiology. TGFβ3 has been established as an important regulator of palatal fusion in mice and it has been shown that TGFβ3-null mice exhibit CP without any other major deformities. However, the genes that regulate cellular decisions and molecular mechanisms maintained by the TGFβ3 pathway throughout palatogenesis are predominantly unexplored. Our objective in this study was to analyze global transcriptome changes within the palate during different gestational ages within TGFβ3 knockout mice to identify TGFβ3-associated genes previously unknown to be associated with the development of cleft palate. We used deep sequencing technology, RNA-Seq, to analyze the transcriptome of TGFβ3 knockout mice at crucial stages of palatogenesis, including palatal growth (E14.5), adhesion (E15.5), and fusion (E16.5).
Results: The overall transcriptome analysis of TGFβ3 wildtype mice (C57BL/6) reveals that almost 6000 genes were upregulated during the transition from E14.5 to E15.5 and more than 2000 were downregulated from E15.5 to E16.5. Using bioinformatics tools and databases, we identified the most comprehensive list of CP genes (n = 322) in which mutations cause CP either in humans or mice, and analyzed their expression patterns. The expression motifs of CP genes between TGFβ3+/− and TGFβ3−/− were not significantly different from each other, and the expression of the majority of CP genes remained unchanged from E14.5 to E16.5. Using these patterns, we identified 8 unique genes within TGFβ3−/− mice (Chrng Foxc2, H19, Kcnj13, Lhx8, Meox2, Shh, and Six3), which may function as the primary contributors to the development of cleft palate in TGFβ3−/− mice. When the significantly altered CP genes were overlaid with TGFβ signaling, all of these genes followed the Smad-dependent pathway.
Conclusions: Our study represents the first analysis of the palatal transcriptome of the mouse, as well as TGFβ3 knockout mice, using deep sequencing methods. In this study, we characterized the critical regulation of palatal transcripts that may play key regulatory roles through crucial stages of palatal development. We identified potential causative CP genes in a TGFβ3 knockout model, which may lead to a better understanding of the genetic mechanisms of palatogenesis and provide novel potential targets for gene therapy approaches to treat cleft palate.
Overall design Palatal mRNA profiles of wild type (WT), TGFβ3+/-, and TGFβ3-/- mice at E14.5, E15.5, and E16.5 were generated by deep sequencing, in triplicate, using Illumina HiSeq2000
Contributor(s) Ozturk F, Li Y, Zhu X, Guda C, Nawshad A
Citation(s) 23421592
Submission date Mar 28, 2013
Last update date Apr 28, 2020
Contact name You Li
Organization name University of Nebraska Medical Center
Department Department of Genetics, Cell Biology and Anatomy
Lab Guda Lab
Street address Emile St
State/province NE
ZIP/Postal code 68198
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (36)
GSM1109819 E14.5 TGFβ3-KO BioRep1 Lane001
GSM1109820 E14.5 TGFβ3-KO BioRep1 Lane002
GSM1109821 E14.5 TGFβ3-KO BioRep2 Lane001
BioProject PRJNA194595
SRA SRP020224

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Supplementary file Size Download File type/resource
GSE45568_G1-T1vsT2_all.xlsx.gz 1.1 Mb (ftp)(http) XLSX
GSE45568_G2-T1vsT2_all.xlsx.gz 614.2 Kb (ftp)(http) XLSX
GSE45568_G3-T1vsT2_all.xlsx.gz 1.4 Mb (ftp)(http) XLSX
GSE45568_RAW.tar 23.4 Mb (http)(custom) TAR (of TXT)
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Processed data provided as supplementary file
Processed data are available on Series record
Raw data are available in SRA

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