Dlx3b/4b-dependent genes in early zebrafish inner ear development
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE220564 | GEO | 2023/05/19
REPOSITORIES: GEO
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Project description:Identification of genes regulated by the distal-less homeodomain transcription factor Atoh1b. To this aim, we performed gene expression profiling analysis using data obtained from RNA-seq of 3 samples each from wt control as well as atoh1b knockdown.
2023-05-19 | GSE220565 | GEO
Project description:Dlx3b/4b-dependent genes in early zebrafish inner ear development
| PRJNA910217 | ENA
Project description:The vertebrate inner ear is the sensory organ mediating hearing and balance. The entire organ develops from the otic placode, which itself originates from the otic-epibranchial progenitor domain (OEPD). Multiple studies in various species have shown the importance of the forkhead-box and distal-less homeodomain transcription factor families for OEPD and subsequent otic placode formation. However, the transcriptional networks downstream of these factors are only beginning to be understood. Using transcriptome analysis, we here reveal numerous genes regulated by the distal-less homeodomain transcription factors Dlx3b and Dlx4b (Dlx3b/4b). We identify known and novel transcripts displaying widespread OEPD expression in a Dlx3b/4b-dependent manner. Some genes, with a known OEPD expression in other vertebrate species, might be members of a presumptive vertebrate core module required for proper otic development. Moreover, we identify genes controlling early-born sensory hair cell formation as well as regulating biomineral tissue development, both consistent with defective sensory hair cell and otolith formation observed in dlx3b/4b mutants. Finally, we show that ectopic Atoh1b expression can rescue early sensorigenesis even in the absence of Dlx3b/4b. Taken together, our data will help to unravel the gene regulatory network underlying early inner ear development and provide insights into the molecular control of vertebrate inner ear formation to restore hearing loss in humans ultimately.
| S-EPMC10261724 | biostudies-literature
Project description:Several transcription factors are known to be expressed in discrete regions of the otic vesicle and Dlx5 is one of those that is expressed highly in the presumptive dorsal vestibular region. Mice lacking Dlx5 have vestibular defects. Specifically, they fail to form the endolymphatic duct (a defect visible as early as E10) as well as the anterior and posterior semi-circular canals. The lateral canal does form but is smaller, whereas the saccule, the utricle and the cochlea appear relatively normal. The goal of this study was to use microarrays to identify differentially expressed genes between wild-type and Dlx5-null otic vesicles microdissected from E10 and 10.5 and identify downstream targets of Dlx5 by searching the immediate 3kb promoter regions of the differentially expressed genes for homeodomain binding sites followed by chromatin immunoprecipitation in an otic vesicle-derived cell line over-expressing Dlx5. Normal vestibular morphogenesis is compromised in mice lacking Dlx5, a member of the Distal-less family of homeobox transcription factors. We identified its direct downstream targets in the developing mouse inner ear by gene expression profiling wild-type and Dlx5 null otic vesicles from embryonic stages E10 and E10.5. Four hundred genes were differentially expressed in mutants when compared to wild-type in at least one of the two stages. To further constrain the list of likely direct targets of Dlx5, we examined the genomic DNA sequences in the 3kb promoter regions immediately proximal to the transcriptional start sites of these genes. We searched for (i) one or more previously described binding site for Dlx5, (ii) one or more novel 12bp-long motifs with a canonical homeodomain response element (HDRE) shared by promoters of two or more genes, and (iii) 100% conservation of the 12bp-long HDRE-containing motifs in promoter regions of human orthologs. Forty genes passed one or more of these filters, 12 of which are known to be expressed in the developing otic vesicle in domains that at least partially overlap with that of Dlx5 in one or both stages that we examined. Chromatin immunoprecipitation using a Dlx5 antibody confirmed direct binding of Dlx5 to promoter regions of seven of these genes (Atbf1, Bmper, Large, Lrrtm1, and Msx1, all of which were down-regulated in mutants, and Ebf1 and Lhx1, both of which were up-regulated in mutants) in an otic vesicle-derived cell line over-expressing Dlx5. Gene expression profiling of this cell line showed that Bmper and Lrrtm1 transcripts were up-regulated, further supporting their identification as direct targets of Dlx5 activity. Otic vesicles from wild-type and Dlx5-null embryos were microdissected from mouse developmental stages E10 and E10.5 and expression profiled in duplicate for each stage and genotype. Dlx5-transfected and empty vector-transfected 2B1 cell line samples were also profiled in duplicate (independent cell cultures).
2011-07-01 | E-GEOD-22381 | biostudies-arrayexpress
Project description:Atoh1b-dependent genes in early zebrafish inner ear development
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Project description:Several transcription factors are known to be expressed in discrete regions of the otic vesicle and Dlx5 is one of those that is expressed highly in the presumptive dorsal vestibular region. Mice lacking Dlx5 have vestibular defects. Specifically, they fail to form the endolymphatic duct (a defect visible as early as E10) as well as the anterior and posterior semi-circular canals. The lateral canal does form but is smaller, whereas the saccule, the utricle and the cochlea appear relatively normal. The goal of this study was to use microarrays to identify differentially expressed genes between wild-type and Dlx5-null otic vesicles microdissected from E10 and 10.5 and identify downstream targets of Dlx5 by searching the immediate 3kb promoter regions of the differentially expressed genes for homeodomain binding sites followed by chromatin immunoprecipitation in an otic vesicle-derived cell line over-expressing Dlx5. Normal vestibular morphogenesis is compromised in mice lacking Dlx5, a member of the Distal-less family of homeobox transcription factors. We identified its direct downstream targets in the developing mouse inner ear by gene expression profiling wild-type and Dlx5 null otic vesicles from embryonic stages E10 and E10.5. Four hundred genes were differentially expressed in mutants when compared to wild-type in at least one of the two stages. To further constrain the list of likely direct targets of Dlx5, we examined the genomic DNA sequences in the 3kb promoter regions immediately proximal to the transcriptional start sites of these genes. We searched for (i) one or more previously described binding site for Dlx5, (ii) one or more novel 12bp-long motifs with a canonical homeodomain response element (HDRE) shared by promoters of two or more genes, and (iii) 100% conservation of the 12bp-long HDRE-containing motifs in promoter regions of human orthologs. Forty genes passed one or more of these filters, 12 of which are known to be expressed in the developing otic vesicle in domains that at least partially overlap with that of Dlx5 in one or both stages that we examined. Chromatin immunoprecipitation using a Dlx5 antibody confirmed direct binding of Dlx5 to promoter regions of seven of these genes (Atbf1, Bmper, Large, Lrrtm1, and Msx1, all of which were down-regulated in mutants, and Ebf1 and Lhx1, both of which were up-regulated in mutants) in an otic vesicle-derived cell line over-expressing Dlx5. Gene expression profiling of this cell line showed that Bmper and Lrrtm1 transcripts were up-regulated, further supporting their identification as direct targets of Dlx5 activity.
2011-07-01 | GSE22381 | GEO
Project description:MiaPaCa2 cells where screened with a set of original compounds with anticancer activity available at our laboratory. From these compounds we identified the nucleoside analogue ly101-4B as a strong inhibitor of the E2F activity. We confirmed its activity by studying its effect on MiaPaCa2's cell viability , caspase 3/7 activity and LDH release, to measure cell growth, apoptosis and necrosis after treatment with LY101-4B 25 µM. Then, to investigate the mechanism of action of ly101-4B we performed a transcriptomic analysis by using an Affymetrix approach (Genechip® Human Gene 1.0 ST Arrays).
2019-02-28 | GSE109853 | GEO