ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/005/SRR9323045/SRR9323045.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/008/SRR9323038/SRR9323038.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/003/SRR9323043/SRR9323043.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/000/SRR9323040/SRR9323040.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/007/SRR9323037/SRR9323037.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/004/SRR9323044/SRR9323044.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/008/SRR9323048/SRR9323048.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/007/SRR9323047/SRR9323047.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/006/SRR9323046/SRR9323046.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/001/SRR9323041/SRR9323041.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/002/SRR9323042/SRR9323042.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR932/009/SRR9323039/SRR9323039.fastq.gzprimaryOK200GenomicsBiological Sciences, University of Delawarehttps://www.ebi.ac.uk/ena/browser/view/PRJNA549507Mus musculusxref:PubMed:31691004FGFR signaling plays important roles in development and disease pathogenesis. FGFR activation initiates phosphorylation-driven signaling cascades, most notably the RAS-RAF-MEK-ERK cascade and the PI3K-AKT cascade. PTEN antagonizes FGFR signaling by reducing both AKT and ERK activation. Lenses lacking FGFR2 exhibit lower levels of ERK and AKT phosphorylation accompanied by abnormally small lenses, widespread apoptosis, and defective fiber cell differentiation. In contrast, simultaneous deletion of both Fgfr2 and Pten restores ERK and AKT activation levels as well as lens size, cell survival and several aspects of fiber cell differentiation. A transcriptomic analysis of mouse lenses lacking Fgfr2, Pten or both Fgfr2 and Pten revealed molecular mechanisms that might explain how FGFR2 and PTEN signaling interact during development. The FGFR2-deficient lens transcriptome suggested an overall loss of fiber cell identity with deregulated expression of 1,448 genes, nearly 60% of which returned to normal expression levels in lenses lacking both Fgfr2 and Pten. A specific set of parameters based on expression levels in each genotype identified 68 high priority candidate genes. The homeobox transcription factor, NKX6-1, encoded by one of these genes, had at least one binding motif in the putative promoters of 53 of these 68 genes. Furthermore, NKX6-1 activated the expression of the high priority candidate Rasgrp1, a RAS-activating guanine nucleotide exchange factor. Together, these data suggest a novel regulatory module in which NKX6-1 activates the expression of Rasgrp1 to restore the balance of ERK and AKT activation in the absence of both FGFR2 and PTEN. Overall design: We collected RNA from the lenses of mice hemizygous for the Le-Cre transgene (control), or hemizygous for Le-Cre and homozygous for loxP flanked (floxed) alleles of Fgfr2, Pten or both Fgfr2/Pten. Lenses were dissected from the eye and carefully isolated from surrounding tissues including the cornea, retina, and tunica vasculosa lentis. Lenses were pooled into three biological replicates for each genotype, with each replicate containing six lenses from three mice.ENADfr1, AU043015, T-cell leukemia, i79, Transcriptome Profile, KGFR, K-SAM, GLM2, CT22273, CFD1, AGL4, DPTEN, Lens <eudicots>, Gene Expression Profile, Gene, Profiles, SEPALLATA 2, Transcription Factor, Uniandra, lens crystallina, CD332, lenses, DmelCG7223, MHAM, zinc ion regulated core promoter proximal region sequence-specific DNA binding, DFGF-R2, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, AI463227, DFGF-R1, FGF-R2, camera-type eye lens, CEK3, TEP1, DFR1, Transcription, AW556123, Profile, copper ion regulated core promoter proximal region sequence-specific binding., ocular lens, crystalline lens, F10N7_150, CT39172, Dfr-1, ECT1, Ect1, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, Signatures, DmelCG5671, Fgfr7, BEK, Bek, Expression Signature, RNA polymerase II proximal promoter sequence-specific DNA binding, DFR-1, FGFR, copper ion regulated proximal promoter sequence-specific DNA binding, Transcriptomes, B430203M17Rik, AGAMOUS-like 4, BFR-1, svs, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, eye lens, Tk1, TRANSCRIPTION FACTOR, FGFR2, single organism signaling, RNA polymerase II distal enhancer sequence-specific binding, Contradens, RNA polymerase II core promoter proximal region sequence-specific binding, lens capsule, Transcriptome, PTEN, DPR3, Expression Profiles, j372, CG7223, dPten, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, Fgfr-7, dtk1, pten, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, Fgfr-2, xfgfr2, whole transcriptome, transcription factor activity, Gene Expression, dpten, JWS, PTEN3, PTEN1, Expression Signatures, CWS1, Gene Expression Signatures, RNA polymerase II transcription factor activity, i150, Gene Expression Signature, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, KSAM, dPTEN, Expression Profile, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, KNOTTED1-like homeobox gene 5, Transcriptome Profiles, HD-38, Htl, F14P3.4, KGFRTr, Fr1, Mmac, EMS2, Factors, 10q23del, CG5671, lens, DFR1/DFGF-R2, MMAC1, BBDS, F14P3_4, i100, A130070J02Rik, metal ion regulated core promoter proximal region sequence-specific binding, PTENa, Transcription factor, TK25, F10N7.150, HTL/FGFR1, DEC, FR1, signalling process, Gene Expression Profiles, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, DmHD-38, Dtk1, Signature, BZS, metal ion regulated sequence-specific DNA binding, DTRK(FR1), Lens <bivalves>, TK14, metal ion regulated proximal promoter sequence-specific DNA binding, 2310035O07RikDfr1, AU043015, T-cell leukemia, i79, Transcriptome Profile, KGFR, K-SAM, GLM2, CT22273, CFD1, AGL4, DPTEN, Lens <eudicots>, Gene Expression Profile, Gene, Profiles, SEPALLATA 2, Transcription Factor, Uniandra, lens crystallina, CD332, lenses, DmelCG7223, MHAM, zinc ion regulated core promoter proximal region sequence-specific DNA binding, DFGF-R2, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, AI463227, DFGF-R1, FGF-R2, camera-type eye lens, CEK3, TEP1, DFR1, Transcription, AW556123, Profile, copper ion regulated core promoter proximal region sequence-specific binding., ocular lens, crystalline lens, F10N7_150, CT39172, Dfr-1, ECT1, Ect1, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, Signatures, DmelCG5671, Fgfr7, BEK, Bek, Expression Signature, RNA polymerase II proximal promoter sequence-specific DNA binding, DFR-1, FGFR, copper ion regulated proximal promoter sequence-specific DNA binding, Transcriptomes, B430203M17Rik, AGAMOUS-like 4, BFR-1, svs, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, eye lens, Tk1, TRANSCRIPTION FACTOR, FGFR2, single organism signaling, RNA polymerase II distal enhancer sequence-specific binding, Contradens, RNA polymerase II core promoter proximal region sequence-specific binding, lens capsule, Transcriptome, PTEN, DPR3, Expression Profiles, j372, CG7223, dPten, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, Fgfr-7, dtk1, pten, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, Fgfr-2, xfgfr2, whole transcriptome, transcription factor activity, Gene Expression, dpten, JWS, PTEN3, PTEN1, Expression Signatures, CWS1, Gene Expression Signatures, RNA polymerase II transcription factor activity, i150, Gene Expression Signature, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, KSAM, dPTEN, Expression Profile, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, KNOTTED1-like homeobox gene 5, Transcriptome Profiles, HD-38, Htl, F14P3.4, KGFRTr, Fr1, Mmac, EMS2, Factors, 10q23del, CG5671, lens, DFR1/DFGF-R2, MMAC1, BBDS, F14P3_4, i100, A130070J02Rik, metal ion regulated core promoter proximal region sequence-specific binding, PTENa, Transcription factor, TK25, F10N7.150, HTL/FGFR1, DEC, FR1, signalling process, Gene Expression Profiles, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, DmHD-38, Dtk1, Signature, BZS, metal ion regulated sequence-specific DNA binding, DTRK(FR1), Lens <bivalves>, TK14, metal ion regulated proximal promoter sequence-specific DNA binding, 2310035O07RikfalseThe developing lens transcriptome depends upon a counterbalance of Fgfr2- and Pten-regulated downstream signaling and transcription factor targetsThe developing lens transcriptome depends upon a counterbalance of Fgfr2- and Pten-regulated downstream signaling and transcription factor targets2025-09-242020-03-24PRJNA549507GSE1329451009031691004