Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BDNF-TrkB axis regulates migration of the lateral line primordium and modulates the maintenance of mechanoreceptor progenitors.

ABSTRACT: BDNF and its specialized receptor TrkB are expressed in the developing lateral line system of zebrafish, but their role in this organ is unknown. To tackle this problem in vivo, we used transgenic animals expressing fluorescent markers in different cell types of the lateral line and combined a BDNF gain-of-function approach by BDNF mRNA overexpression and by soaking embryos in a solution of BDNF, with a loss-of-function approach by injecting the antisence ntrk2b-morpholino and treating embryos with the specific Trk inhibitor K252a. Subsequent analysis demonstrated that the BDNF-TrkB axis regulates migration of the lateral line primordium. In particular, BDNF-TrkB influences the expression level of components of chemokine signaling including Cxcr4b, and the generation of progenitors of mechanoreceptors, at the level of expression of Atoh1a-Atp2b1a.

SUBMITTER: Gasanov EV

PROVIDER: S-EPMC4353718 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

BDNF-TrkB axis regulates migration of the lateral line primordium and modulates the maintenance of mechanoreceptor progenitors.

Gasanov Eugene V EV Rafieva Lola M LM Korzh Vladimir P VP

PloS one 20150309 3

BDNF and its specialized receptor TrkB are expressed in the developing lateral line system of zebrafish, but their role in this organ is unknown. To tackle this problem in vivo, we used transgenic animals expressing fluorescent markers in different cell types of the lateral line and combined a BDNF gain-of-function approach by BDNF mRNA overexpression and by soaking embryos in a solution of BDNF, with a loss-of-function approach by injecting the antisence ntrk2b-morpholino and treating embryos w ...[more]

PMID: 25751404

Similar Datasets

Stat3-Bdnf-TrkB axis promotes alveolar regeneration

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-06-01 | GSE132535 | GEO

Stat3-Bdnf-TrkB axis promotes alveolar regeneration [ATAC-seq]

Project description:Regenerating new alveolar epithelium is essential for recovery from many lung diseases. This multi-cellular regenerative process occurs when type II alveolar pneumocytes (AT2), with support from mesenchymal niche cells, proliferate to generate more AT2 cells and transdifferentiate in type I pneumocytes. To elucidate how coordinated events between AT2 cells and mesenchyme restore alveolar epithelium we used unbiased genome-wide analysis of chromatin accessibility and gene expression in both cell types following acute lung injury. We observed that chromatin acessability in AT2 cells changes signficantly following acute lung injury. Newly accessible chromatin reveals new STAT3 binding motifs adjacent to genes that regulate essential regenerative pathways in AT2 cells. Restoration of alveolar structures following both sterile and infectious lung injuries was inhibited when STAT3 signaling was lost in AT2 cells. Single-cell transcriptome analysis of regenerating AT2 cells identified brain neurotrophic factor (Bdnf) as the sole STAT3 target gene whose chromatin becomes newly accessible in a regenerating population of AT2 cells. BDNF increased alveolar organoid size and forming efficiency in murine and human models. The receptor for BDNF, TrkB, is uniquely? expressed on mesenchymal alveolar niche cells (MANC). Exposure of BDNF to TrkB increases expression of fibroblast growth factor 7 (Fgf7), an essential regenerative cytokine, in MANCs. Blocking Bdnf signaling with a TrkB receptor antagonist abrogated murine and human alveolar organoid formation. Finally, a small molecule TrkB agonist improved functional and histological outcomes in vivo following sterile and infectious lung injuries. Collectively, these data highlight the biological and therapeutic importance of the Stat3-Bdnf-TrkB axis in orchestrating alveolar epithelial regeneration

2020-06-01 | GSE132534 | GEO

Stat3-Bdnf-TrkB axis promotes alveolar regeneration [scRNA-seq]

2020-06-01 | GSE132533 | GEO

Transcriptome profiles of sturgeon lateral line electroreceptor and mechanoreceptor during regeneration.

Project description:BackgroundThe electrosensory ampullary organs (AOs) and mechanosensory neuromasts (NMs) found in sturgeon and some other non-neopterygian fish or amphibians are both originated from lateral line placodes. However, these two sensory organs have characteristic morphological and physiological differences. The molecular mechanisms for the specification of AOs and NMs are not clearly understood.ResultsWe sequenced the transcriptome for neomycin treated sturgeon AOs and NMs in the early regeneration stages, and de novo assembled a sturgeon transcriptome. By comparing the gene expression differences among untreated AOs, NMs and general epithelia (EPs), we located some specific genes for these two sensory organs. In sturgeon lateral line, the voltage-gated calcium channels and voltage-gated potassium channels were predominant calcium and potassium channel subtypes, respectively. And by correlating gene expression with the regeneration process, we predicated several candidate key transcriptional regulation related genes might be involved in AOs and NMs regeneration.ConclusionsGenes with specific expression in the two lateral line sensory organs suggests their important roles in mechanoreceptor and electroreceptor formation. The candidate transcriptional regulation related genes may be important for mechano- and electro- receptor specification, in a "dosage-related" manner. These results suggested the molecular basis for specification of these two sensory organs in sturgeon.

| S-EPMC7720607 | biostudies-literature

Stat3-Bdnf-TrkB axis promotes alveolar regeneration

Project description:Stat3-Bdnf-TrkB axis promotes alveolar regeneration

| PRJNA548314 | ENA

Transcriptome profiles of sturgeon lateral line electroreceptor and mechanoreceptor during regeneration

Project description:The larvae were treated with 200 μM neomycin to deplete the hair cells in neuromast and ampullary organ. Two kinds of sensory epithelia at the ventral side of head were separated at 12 hour-post treatment (hpt) and 24 hpt, respectively. Mechano- and electro- sensory epithelia before neomycin treating were collected respectively as control (untreated).The epithelia near but without two kinds of sensors (EPs) were also collected. Total RNAs were extracted by TRIzol (Invitrogen) using standard protocols. RNA libraries were prepared by TruSeq RNA Sample Prep Kit (Illumina), following the manufacturer's instructions.

2020-12-15 | GSE151096 | GEO

Molecular dissection of the migrating posterior lateral line primordium during early development in zebrafish.

Project description:Development of the posterior lateral line (PLL) system in zebrafish involves cell migration, proliferation and differentiation of mechanosensory cells. The PLL forms when cranial placodal cells delaminate and become a coherent, migratory primordium that traverses the length of the fish to form this sensory system. As it migrates, the primordium deposits groups of cells called neuromasts, the specialized organs that contain the mechanosensory hair cells. Therefore the primordium provides both a model for studying collective directional cell migration and the differentiation of sensory cells from multipotent progenitor cells.Through the combined use of transgenic fish, Fluorescence Activated Cell Sorting and microarray analysis we identified a repertoire of key genes expressed in the migrating primordium and in differentiated neuromasts. We validated the specific expression in the primordium of a subset of the identified sequences by quantitative RT-PCR, and by in situ hybridization. We also show that interfering with the function of two genes, f11r and cd9b, defects in primordium migration are induced. Finally, pathway construction revealed functional relationships among the genes enriched in the migrating cell population.Our results demonstrate that this is a robust approach to globally analyze tissue-specific expression and we predict that many of the genes identified in this study will show critical functions in developmental events involving collective cell migration and possibly in pathological situations such as tumor metastasis.

| S-EPMC3016277 | biostudies-literature

Lef1 is required for progenitor cell identity in the zebrafish lateral line primordium.

Project description:The zebrafish posterior lateral line (pLL) is a sensory system that comprises clusters of mechanosensory organs called neuromasts (NMs) that are stereotypically positioned along the surface of the trunk. The NMs are deposited by a migrating pLL primordium, which is organized into polarized rosettes (proto-NMs). During migration, mature proto-NMs are deposited from the trailing part of the primordium, while progenitor cells in the leading part give rise to new proto-NMs. Wnt signaling is active in the leading zone of the primordium and global Wnt inactivation leads to dramatic disorganization of the primordium and a loss of proto-NM formation. However, the exact cellular events that are regulated by the Wnt pathway are not known. We identified a mutant strain, lef1(nl2), that contains a lesion in the Wnt effector gene lef1. lef1(nl2) mutants lack posterior NMs and live imaging reveals that rosette renewal fails during later stages of migration. Surprisingly, the overall primordium patterning, as assayed by the expression of various markers, appears unaltered in lef1(nl2) mutants. Lineage tracing and mosaic analyses revealed that the leading cells (presumptive progenitors) move out of the primordium and are incorporated into NMs; this results in a decrease in the number of proliferating progenitor cells and eventual primordium disorganization. We concluded that Lef1 function is not required for initial primordium organization or migration, but is necessary for proto-NM renewal during later stages of pLL formation. These findings revealed a novel role for the Wnt signaling pathway during mechanosensory organ formation in zebrafish.

| S-EPMC3160089 | biostudies-other

Leading and trailing cells cooperate in collective migration of the zebrafish posterior lateral line primordium.

Project description:Collective migration of cells in the zebrafish posterior lateral line primordium (PLLp) along a path defined by Cxcl12a expression depends on Cxcr4b receptors in leading cells and on Cxcr7b in trailing cells. Cxcr7b-mediated degradation of Cxcl12a by trailing cells generates a local gradient of Cxcl12a that guides PLLp migration. Agent-based computer models were built to explore how a polarized response to Cxcl12a, mediated by Cxcr4b in leading cells and prevented by Cxcr7b in trailing cells, determines unidirectional migration of the PLLp. These chemokine signaling-based models effectively recapitulate many behaviors of the PLLp and provide potential explanations for the characteristic behaviors that emerge when the PLLp is severed by laser to generate leading and trailing fragments. As predicted by our models, the bilateral stretching of the leading fragment is lost when chemokine signaling is blocked in the PLLp. However, movement of the trailing fragment toward the leading cells, which was also thought to be chemokine dependent, persists. This suggested that a chemokine-independent mechanism, not accounted for in our models, is responsible for this behavior. Further investigation of trailing cell behavior shows that their movement toward leading cells depends on FGF signaling and it can be re-oriented by exogenous FGF sources. Together, our observations reveal the simple yet elegant manner in which leading and trailing cells coordinate migration; while leading cells steer PLLp migration by following chemokine cues, cells further back play follow-the-leader as they migrate toward FGFs produced by leading cells.

| S-EPMC4197546 | biostudies-literature

Lef1 regulates Dusp6 to influence neuromast formation and spacing in the zebrafish posterior lateral line primordium.

Project description:The posterior lateral line primordium (PLLp) migrates caudally and periodically deposits neuromasts. Coupled, but mutually inhibitory, Wnt-FGF signaling systems regulate proto-neuromast formation in the PLLp: FGF ligands expressed in response to Wnt signaling activate FGF receptors and initiate proto-neuromast formation. FGF receptor signaling, in turn, inhibits Wnt signaling. However, mechanisms that determine periodic neuromast formation and deposition in the PLLp remain poorly understood. Previous studies showed that neuromasts are deposited closer together and the PLLp terminates prematurely in lef1-deficient zebrafish embryos. It was suggested that this results from reduced proliferation in the leading domain of the PLLp and/or premature incorporation of progenitors into proto-neuromasts. We found that rspo3 knockdown reduces proliferation in a manner similar to that seen in lef1 morphants. However, it does not cause closer neuromast deposition or premature termination of the PLLp, suggesting that such changes in lef1-deficient embryos are not linked to changes in proliferation. Instead, we suggest that they are related to the role of Lef1 in regulating the balance of Wnt and FGF functions in the PLLp. Lef1 determines expression of the FGF signaling inhibitor Dusp6 in leading cells and regulates incorporation of cells into neuromasts; reduction of Dusp6 in leading cells in lef1-deficient embryos allows new proto-neuromasts to form closer to the leading edge. This is associated with progressively slower PLLp migration, reduced spacing between deposited neuromasts and premature termination of the PLLp system.

| S-EPMC3653559 | 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