GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE51374 Query DataSets for GSE51374
Status Public on Sep 25, 2018
Title Meis genes regulate RA/FGF signaling to control multiple steps of limb development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Vertebrate limbs develop by integrating signals that control patterning along three main orthogonal axes. Flank-produced retinoic acid (RA) is initially required for limb induction and establishment of the apical ectodermal ridge (AER), a distal signaling center that produces fibroblast growth factors (FGFs), which are essential for limb growth and distalization. Once the AER is established, RA:FGF antagonism determines the restricted expression of a set of genes that control limb proximodistal patterning. Essential for this antagonism is the activation by FGF of the RA-degrading enzyme CYP26B1 in the distal limb bud. In addition, sonic hedgehog produced from the zone of polarizing activity (ZPA) is essential for distal limb anteroposterior patterning and contributes to RA reduction by cooperating in CYP26B1 activation. Meis transcription factors are expressed in the proximal limb bud, are activated by RA and can regulate proximodistal limb development; however, the mechanisms underlying their activity remain unknown. Here we studied Meis function in the mouse limb bud through Meis2 conditional overexpression and elimination of Meis1 and Meis2. We found that Meis activity is first required for limb bud initiation and the proper establishment of the AER and ZPA signaling centers, and subsequently for the development of proximal limb structures. Functional genomic analyses reveal that Meis is an important conveyor of the RA:FGF antagonism through the regulation of components of the RA and FGF signaling pathways, including CYP26B1. In addition, Meis regulates a set of proximal limb genes controlling proximodistal patterning and differentiation. Our work reveals a regulatory module essential for limb patterning and potentially co-opted in other patterning processes involving RA:FGF antagonism.
Overall design Examination of gene profile on distal limb bud tips of mice overexpressing Meis2
Contributor(s) Roselló-Diez A, Torres M
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Oct 17, 2013
Last update date May 15, 2019
Contact name Carlos Torroja
Phone (+34) 91 4531200
Organization name Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Department Bioinformatics Unit
Street address Melchor Fernandez Almagro, 3
City Madrid
State/province Madrid
ZIP/Postal code 28029
Country Spain
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (6)
GSM1244091 Control1_37so
GSM1244092 Control2_38so
GSM1244093 Control3_39so
BioProject PRJNA222847
SRA SRP031465

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE51374_normalized_matrix_table.xlsx.gz 1.1 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap