Epigenetic and transcriptomic signature reveals Sox8 as an otic master regulator
Ontology highlight
ABSTRACT:
ORGANISM(S): Gallus gallus
PROVIDER: GSE102825 | GEO | 2022/08/01
REPOSITORIES: GEO
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Project description:The inner ear develops from a patch of thickened cranial ectoderm adjacent to the hindbrain called the otic placode. Studies in a number of vertebrate species suggest that the initial steps in induction of the otic placode are regulated by members of the Fibroblast Growth Factor (FGF) family, and that inhibition of FGF signaling can prevent otic placode formation. To better understand the genetic pathways activated by FGF signaling during otic placode induction, we performed microarray experiments to estimate the proportion of chicken otic placode genes that can be up-regulated by the FGF pathway in a simple culture model of otic placode induction. Surprisingly, we find that FGF is only sufficient to induce about 15% of chick otic placode-specific genes in our experimental system. However, pharmacological blockade of the FGF pathway in cultured chick embryos showed that although FGF signaling was not sufficient to induce the majority of otic placode-specific genes, it was still necessary for their expression in vivo. These inhibitor experiments further suggest that the early steps in otic placode induction regulated by FGF signaling occur through the MAP kinase pathway. Although our work suggests that FGF signaling is necessary for otic placode induction, it demonstrates that other unidentified signaling pathways are required to co-operate with FGF signaling to induce the full otic placode program. 8 samples were analyzed. These contain two replicates of each of the following four catergories: Otic ectoderm, Non-Otic (lateral) ectoderm, Trigeminal Ectoderm cultured - FGF, Trigeminal Ectoderm cultured + FGF
2012-12-12 | E-GEOD-42845 | biostudies-arrayexpress
Project description:The otic placode, from which the inner ear develops, initially forms as a thickened ectodermal patch adjacent to the dorsolateral hindbrain. Induction of otic placodal cells from human pluripotent stem cells (hPSCs) provides a robust approach to investigation of otic development. However, attempts to recapitulate otic lineage specification from hPSCs by stepwise differentiation methods have had limited success. One possible reason is that the role of signaling pathways in otic cell differentiation is not fully understood. Here, we developed a novel differentiation system involving use of suspension culture (3D floating culture) in combination with signaling factors for generating otic placodal cells via stepwise differentiation of hPSCs. We demonstrate that hPSC-derived pre-placodal cells acquired the potential to differentiate into posterior placodal cells after fibroblast growth factor 2 (FGF2) and retinoic acid (RA) treatment. Subsequent activation of WNT signaling following posterior placode specification induced differentiation of SIX1+/PAX8+/SOX2+ otic placodal cells. qPCR analysis showed that WNT activation increased expression of otocyst markers, including PAX8, PAX2, DLX5 and FBXO2. Moreover, induced otic cells exhibited similar gene expression patterns to the ventral and medial portions of the otocyst that give rise to the sensory epithelium of the inner ear. Collectively, our results indicate a critical role for FGF2, RA, and WNT signaling for the in vitro differentiation of the otic cell lineage from hPSCs. Our new culture system paves the way for improved modeling of early human inner ear development and will be of value to studies on the further differentiation of sensory epithelial cells.
2022-02-01 | GSE175998 | GEO
Project description:The inner ear develops from a patch of thickened cranial ectoderm adjacent to the hindbrain called the otic placode. Studies in a number of vertebrate species suggest that the initial steps in induction of the otic placode are regulated by members of the Fibroblast Growth Factor (FGF) family, and that inhibition of FGF signaling can prevent otic placode formation. To better understand the genetic pathways activated by FGF signaling during otic placode induction, we performed microarray experiments to estimate the proportion of chicken otic placode genes that can be up-regulated by the FGF pathway in a simple culture model of otic placode induction. Surprisingly, we find that FGF is only sufficient to induce about 15% of chick otic placode-specific genes in our experimental system. However, pharmacological blockade of the FGF pathway in cultured chick embryos showed that although FGF signaling was not sufficient to induce the majority of otic placode-specific genes, it was still necessary for their expression in vivo. These inhibitor experiments further suggest that the early steps in otic placode induction regulated by FGF signaling occur through the MAP kinase pathway. Although our work suggests that FGF signaling is necessary for otic placode induction, it demonstrates that other unidentified signaling pathways are required to co-operate with FGF signaling to induce the full otic placode program.
2012-12-12 | GSE42845 | GEO
Project description:The vertebrate inner ear arises from a pool of progenitors with the potential to give rise to all the sense organs and cranial ganglia of the head1-6. Here we explore the molecular mechanisms that control ear specification from these progenitors. Using a multi-omics approach combined with loss-of-function experiments we identify a core transcriptional circuit that imparts ear identity, along with non-coding elements that integrate this information. This analysis places the transcription factor Sox8 at the top of the ear determination network. Introducing Sox8 into cranial ectoderm not only converts non-ear cells into ear progenitors, but also activates the cellular programmes for ear morphogenesis and neurogenesis. Thus, Sox8 emerges as a master regulator of ear identity and may be a key factor for sense organ cell reprogramming.
2022-07-06 | GSE168088 | GEO
Project description:The vertebrate inner ear arises from a pool of progenitors with the potential to give rise to all the sense organs and cranial ganglia of the head1-6. Here we explore the molecular mechanisms that control ear specification from these progenitors. Using a multi-omics approach combined with loss-of-function experiments we identify a core transcriptional circuit that imparts ear identity, along with non-coding elements that integrate this information. This analysis places the transcription factor Sox8 at the top of the ear determination network. Introducing Sox8 into cranial ectoderm not only converts non-ear cells into ear progenitors, but also activates the cellular programmes for ear morphogenesis and neurogenesis. Thus, Sox8 emerges as a master regulator of ear identity and may be a key factor for sense organ cell reprogramming.
2022-07-06 | GSE168087 | GEO
Project description:The vertebrate inner ear arises from a pool of progenitors with the potential to give rise to all the sense organs and cranial ganglia of the head1-6. Here we explore the molecular mechanisms that control ear specification from these progenitors. Using a multi-omics approach combined with loss-of-function experiments we identify a core transcriptional circuit that imparts ear identity, along with non-coding elements that integrate this information. This analysis places the transcription factor Sox8 at the top of the ear determination network. Introducing Sox8 into cranial ectoderm not only converts non-ear cells into ear progenitors, but also activates the cellular programmes for ear morphogenesis and neurogenesis. Thus, Sox8 emerges as a master regulator of ear identity and may be a key factor for sense organ cell reprogramming.
2022-07-06 | GSE168084 | GEO
Project description:The vertebrate inner ear arises from a pool of progenitors with the potential to give rise to all the sense organs and cranial ganglia of the head1-6. Here we explore the molecular mechanisms that control ear specification from these progenitors. Using a multi-omics approach combined with loss-of-function experiments we identify a core transcriptional circuit that imparts ear identity, along with non-coding elements that integrate this information. This analysis places the transcription factor Sox8 at the top of the ear determination network. Introducing Sox8 into cranial ectoderm not only converts non-ear cells into ear progenitors, but also activates the cellular programmes for ear morphogenesis and neurogenesis. Thus, Sox8 emerges as a master regulator of ear identity and may be a key factor for sense organ cell reprogramming.
2022-07-06 | GSE168082 | GEO
Project description:The vertebrate inner ear arises from a pool of progenitors with the potential to give rise to all the sense organs and cranial ganglia of the head1-6. Here we explore the molecular mechanisms that control ear specification from these progenitors. Using a multi-omics approach combined with loss-of-function experiments we identify a core transcriptional circuit that imparts ear identity, along with non-coding elements that integrate this information. This analysis places the transcription factor Sox8 at the top of the ear determination network. Introducing Sox8 into cranial ectoderm not only converts non-ear cells into ear progenitors, but also activates the cellular programmes for ear morphogenesis and neurogenesis. Thus, Sox8 emerges as a master regulator of ear identity and may be a key factor for sense organ cell reprogramming.
2022-07-06 | GSE168083 | GEO
Project description:Specification of Sox2+ pro-neurosensory progenitors within otic ectoderm is a prerequisite for the production of sensory cells and neurons for hearing. However, the underlying molecular mechanisms driving this lineage specification remain unknown. Here, we show that Brg1-based SWI/SNF chromatin-remodeling complex interacts with the neurosensory-specific transcriptional regulators Eya1/Six1 to induce Sox2 expression and promote pro-neurosensory-lineage specification. Ablation of the ATPase-subunit Brg1 or both Eya1/Six1 results in loss of Sox2 expression and lack of neurosensory identity, leading to abnormal apoptosis within the otic ectoderm. Brg1 binds to two of three distal 3' Sox2 enhancers occupied by Six1, and Brg1-binding to these regions depends on Eya1-Six1 activity. We demonstrate that the activity of these Sox2 enhancers in otic neurosensory cells specifically depends on binding to Six1. Furthermore, genome-wide and transcriptome profiling indicate that Brg1 may suppress apoptotic factor Map3k5 to inhibit apoptosis. Together, our findings reveal an essential role for Brg1, its downstream pathways, and their interactions with Six1/Eya1, in promoting pro-neurosensory fate induction in the otic ectoderm and subsequent neuronal lineage commitment and survival of otic cells.
2021-06-04 | GSE166588 | GEO
Project description:Sox8 reprogram ectoderm into ear vesicles and auditory neurons
| PRJNA706400 | ENA