Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear.

ABSTRACT: Vertebrate hearing and balance are based in complex asymmetries of inner ear structure. Here, we identify retinoic acid (RA) as an extrinsic signal that acts directly on the ear rudiment to affect its compartmentalization along the anterior-posterior axis. A rostrocaudal wave of RA activity, generated by tissues surrounding the nascent ear, induces distinct responses from anterior and posterior halves of the inner ear rudiment. Prolonged response to RA by posterior otic tissue correlates with Tbx1 transcription and formation of mostly nonsensory inner ear structures. By contrast, anterior otic tissue displays only a brief response to RA and forms neuronal elements and most sensory structures of the inner ear.

SUBMITTER: Bok J

PROVIDER: S-EPMC3017143 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear.

Bok Jinwoong J Raft Steven S Kong Kyoung-Ah KA Koo Soo Kyung SK Dräger Ursula C UC Wu Doris K DK

Proceedings of the National Academy of Sciences of the United States of America 20101220 1

Vertebrate hearing and balance are based in complex asymmetries of inner ear structure. Here, we identify retinoic acid (RA) as an extrinsic signal that acts directly on the ear rudiment to affect its compartmentalization along the anterior-posterior axis. A rostrocaudal wave of RA activity, generated by tissues surrounding the nascent ear, induces distinct responses from anterior and posterior halves of the inner ear rudiment. Prolonged response to RA by posterior otic tissue correlates with Tb ...[more]

PMID: 21173260

Similar Datasets

Retinoic acid repression of bone morphogenetic protein 4 in inner ear development.

Project description:Bone morphogenetic protein 4 (BMP4) and retinoic acid are important for normal development of the inner ear, but whether they are linked mechanistically is not known. BMP4 antagonists disrupt semicircular canal formation, as does exposure to retinoic acid. We demonstrate that retinoic acid directly down-regulates BMP4 transcription in a mouse inner ear-derived cell line, and we identify a novel promoter in the second intron of the BMP4 gene that is a target of this regulation both in the cell line and in the mouse embryonic inner ear in vivo. The importance of this down-regulation is demonstrated in chicken embryos by showing that the retinoic acid effect on semicircular canal development can be overcome by exogenous BMP4.

| S-EPMC150746 | biostudies-literature

CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear development.

Project description:CHD7, an ATP-dependent chromatin remodeler, is disrupted in CHARGE syndrome, an autosomal dominant disorder characterized by variably penetrant abnormalities in craniofacial, cardiac, and nervous system tissues. The inner ear is uniquely sensitive to CHD7 levels and is the most commonly affected organ in individuals with CHARGE. Interestingly, upregulation or downregulation of retinoic acid (RA) signaling during embryogenesis also leads to developmental defects similar to those in CHARGE syndrome, suggesting that CHD7 and RA may have common target genes or signaling pathways. Here, we tested three separate potential mechanisms for CHD7 and RA interaction: (a) direct binding of CHD7 with RA receptors, (b) regulation of CHD7 levels by RA, and (c) CHD7 binding and regulation of RA-related genes. We show that CHD7 directly regulates expression of Aldh1a3, the gene encoding the RA synthetic enzyme ALDH1A3 and that loss of Aldh1a3 partially rescues Chd7 mutant mouse inner ear defects. Together, these studies indicate that ALDH1A3 acts with CHD7 in a common genetic pathway to regulate inner ear development, providing insights into how CHD7 and RA regulate gene expression and morphogenesis in the developing embryo.

| S-EPMC5916250 | biostudies-literature

Planarian Hedgehog/Patched establishes anterior-posterior polarity by regulating Wnt signaling.

Project description:Despite long-standing interest, the molecular mechanisms underlying the establishment of anterior-posterior (AP) polarity remain among the unsolved mysteries in metazoans. In the planarians (a family of flatworms), canonical Wnt/beta-catenin signaling is required for posterior specification, as it is in many animals. However, the molecular mechanisms regulating the posterior-specific induction of Wnt genes according to the AP polarity have remained unclear. Here, we demonstrate that Hedgehog (Hh) signaling is responsible for the establishment of AP polarity via its regulation of the transcription of Wnt family genes during planarian regeneration. We found that RNAi gene knockdown of Dugesia japonica patched (Djptc) caused ectopic tail formation in the anterior blastema of body fragments, resulting in bipolar-tails regeneration. In contrast, RNAi of hedgehog (Djhh) and gli (Djgli) caused bipolar-heads regeneration. We show that Patched-mediated Hh signaling was crucial for posterior specification, which is established by regulating the transcription of Wnt genes via downstream Gli activity. Moreover, differentiated cells were responsible for the posterior specification of undifferentiated stem cells through Wnt/beta-catenin signaling. Surprisingly, Djhh was expressed in neural cells all along the ventral nerve cords (along the AP axis), but not in the posterior blastema of body fragments, where the expression of Wnt genes was induced for posteriorization. We therefore propose that Hh signals direct head or tail regeneration according to the AP polarity, which is established by Hh signaling activity along the body's preexisting nervous system.

| S-EPMC2799762 | biostudies-literature

Identification of putative retinoic acid target genes downstream of mesenchymal Tbx1 during inner ear development.

Project description:The T-box transcription factor Tbx1 is expressed in the otic vesicle and surrounding mesoderm of the periotic mesenchyme (POM) during inner ear development. Mesenchymal Tbx1 is essential for inner ear development, with conditional mutants displaying defects in both the auditory and vestibular systems. We have previously reported that mesodermal Tbx1 loss of function mutants (Mest-KO) have reduced expression of retinoic acid (RA) metabolic genes, Cyp26a1 and Cyp26c1, in the POM, consistent with other studies showing an increase in mesodermal RA reporter expression in Tbx1-/- embryos. However, putative RA effector genes whose expression is altered downstream of increased otic mesenchymal-epithelial RA signaling have remained elusive.Here we report the identification of 18 retinoic acid responsive genes altered in Mest-KO conditional mutants by microarray gene profiling. Nine were chosen for biological validation including quantitative RT-PCR and in situ hybridization (Otor, Mia, Col2a1, Clu, Adm, Myt1, Dlx3, Itgb3, and Itga2b).Here study provides a series of newly identified RA effector genes for inner ear development downstream of mesenchymal Tbx1 that may contribute to the inner ear phenotype observed in Tbx1 loss of function mouse models.

| S-EPMC3282991 | biostudies-literature

Retinoic acid synthesis and autoregulation mediate zonal patterning of vestibular organs and inner ear morphogenesis.

Project description:Retinoic acid (RA), a vitamin A (retinol) derivative, has pleiotropic functions during embryonic development. The synthesis of RA requires two enzymatic reactions: oxidation of retinol into retinaldehyde by alcohol dehydrogenases (ADHs) or retinol dehydrogenases (RDHs); and oxidation of retinaldehyde into RA by aldehyde dehydrogenases family 1, subfamily A (ALDH1as), such as ALDH1a1, ALDH1a2 and ALDH1a3. Levels of RA in tissues are regulated by spatiotemporal expression patterns of genes encoding RA-synthesizing and -degrading enzymes, such as cytochrome P450 26 (Cyp26 genes). Here, we show that RDH10 is important for both sensory and non-sensory formation of the vestibule of the inner ear. Mice deficient in Rdh10 exhibit failure of utricle-saccule separation, otoconial formation and zonal patterning of vestibular sensory organs. These phenotypes are similar to those of Aldh1a3 knockouts, and the sensory phenotype is complementary to that of Cyp26b1 knockouts. Together, these results demonstrate that RDH10 and ALDH1a3 are the key RA-synthesis enzymes involved in vestibular development. Furthermore, we discovered that RA induces Cyp26b1 expression in the developing vestibular sensory organs, which generates the differential RA signaling required for zonal patterning.

| S-EPMC7420839 | biostudies-literature

CHD7 and retinoic acid signaling cooperate to regulate neural stem cell and inner ear development in mouse models of CHARGE syndrome.

Project description:CHARGE syndrome is a multiple congenital anomaly disorder that leads to life-threatening birth defects, such as choanal atresia and cardiac malformations as well as multiple sensory impairments, that affect hearing, vision, olfaction and balance. CHARGE is caused by heterozygous mutations in CHD7, which encodes an ATP-dependent chromatin remodeling enzyme. Identification of the mechanisms underlying neurological and sensory defects in CHARGE is a first step toward developing treatments for CHARGE individuals. Here, we used mouse models of Chd7 deficiency to explore the function of CHD7 in the development of the subventricular zone (SVZ) neural stem cell niche and inner ear, structures that are important for olfactory bulb neurogenesis and hearing and balance, respectively. We found that loss of Chd7 results in cell-autonomous proliferative, neurogenic and self-renewal defects in the perinatal and mature mouse SVZ stem cell niche. Modulation of retinoic acid (RA) signaling prevented in vivo inner ear and in vitro neural stem cell defects caused by Chd7 deficiency. Our findings demonstrate critical, cooperative roles for RA and CHD7 in SVZ neural stem cell function and inner ear development, suggesting that altered RA signaling may be an effective method for treating Chd7 deficiency.

| S-EPMC3869363 | biostudies-literature

CHD7 functions upstream of the retinoic acid synthetase ALDH1A3 to regulate inner ear development

Project description:CHD7, an ATP-dependent chromatin remodeler, is disrupted in CHARGE syndrome, an autosomal dominant condition characterized by variably penetrant abnormalities in craniofacial, cardiac, and neuronal tissues. The inner ear is uniquely sensitive to CHD7 levels and is the most commonly affected organ in individuals with CHARGE. Interestingly, up- or down-regulation of retinoic acid (RA) signaling during embryogenesis leads to developmental defects similar to those in CHARGE syndrome, suggesting CHD7 and RA share target genes or signaling pathways. Here, we report that CHD7 and retinoic acid receptor (RAR) do not directly interact, and that RA induces rapid neuronal differentiation of human SH-SY5Y neuroblastoma cells without affecting CHD7 levels. Instead, we provide evidence that CHD7 directly regulates expression of Aldh1a3, which encodes an RA synthetic enzyme, and that loss of Aldh1a3 partially rescues Chd7-mutant mouse inner ear defects, indicating that ALDH1A3 acts with CHD7 in a common genetic pathway to regulate inner ear development.

2020-08-30 | GSE103288 | GEO

Wnt/planar cell polarity signaling controls the anterior-posterior organization of monoaminergic axons in the brainstem.

Project description:Monoaminergic neurons [serotonergic (5-HT) and dopaminergic (mdDA)] in the brainstem project axons along the anterior-posterior axis. Despite their important physiological functions and implication in disease, the molecular mechanisms that dictate the formation of these projections along the anterior-posterior axis remain unknown. Here we reveal a novel requirement for Wnt/planar cell polarity signaling in the anterior-posterior organization of the monoaminergic system. We find that 5-HT and mdDA axons express the core planar cell polarity components Frizzled3, Celsr3, and Vangl2. In addition, monoaminergic projections show anterior-posterior guidance defects in Frizzled3, Celsr3, and Vangl2 mutant mice. The only known ligands for planar cell polarity signaling are Wnt proteins. In culture, Wnt5a attracts 5-HT but repels mdDA axons, and Wnt7b attracts mdDA axons. However, mdDA axons from Frizzled3 mutant mice are unresponsive to Wnt5a and Wnt7b. Both Wnts are expressed in gradients along the anterior-posterior axis, consistent with their role as directional cues. Finally, Wnt5a mutants show transient anterior-posterior guidance defects in mdDA projections. Furthermore, we observe during development that the cell bodies of migrating descending 5-HT neurons eventually reorient along the direction of their axons. In Frizzled3 mutants, many 5-HT and mdDA neuron cell bodies are oriented abnormally along the direction of their aberrant axon projections. Overall, our data suggest that Wnt/planar cell polarity signaling may be a global anterior-posterior guidance mechanism that controls axonal and cellular organization beyond the spinal cord.

| S-EPMC3073573 | biostudies-literature

Dystroglycan down-regulation links EGF receptor signaling and anterior-posterior polarity formation in the Drosophila oocyte.

Project description:Anterior-posterior axis formation in the Drosophila oocyte requires activation of the EGF receptor (EGFR) pathway in the posterior follicle cells (PFC), where it also redirects them from the default anterior to the posterior cell fate. The relationship between EGFR activity in the PFC and oocyte polarity is unclear, because no EGFR-induced changes in the PFC have been observed that subsequently affect oocyte polarity. Here, we show that an extracellular matrix receptor, Dystroglycan, is down-regulated in the PFC by EGFR signaling, and this down-regulation is necessary for proper localization of posterior polarity determinants in the oocyte. Failure to down-regulate Dystroglycan disrupts apicobasal polarity in the PFC, which includes mislocalization of the extracellular matrix component Laminin. Our data indicate that Dystroglycan links EGFR-induced repression of the anterior follicle cell fate and anterior-posterior polarity formation in the oocyte.

| S-EPMC1568923 | biostudies-literature

Latrophilin signaling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo.

Project description:Understanding the mechanisms that coordinate the orientation of cell division planes during embryogenesis and morphogenesis is a fundamental problem in developmental biology. Here we show that the orphan receptor lat-1, a homolog of vertebrate latrophilins, plays an essential role in the establishment of tissue polarity in the C. elegans embryo. We provide evidence that lat-1 is required for the alignment of cell division planes to the anterior-posterior axis and acts in parallel to known polarity and morphogenesis signals. lat-1 is a member of the Adhesion-GPCR protein family and is structurally related to flamingo/CELSR, an essential component of the planar cell polarity pathway. We dissect the molecular requirements of lat-1 signaling and implicate lat-1 in an anterior-posterior tissue polarity pathway in the premorphogenesis stage of C. elegans development.

| S-EPMC2819344 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data