Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA222847 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1012600.fastq.gz | Fastqsanger.gz | |||
| SRR1012601.fastq.gz | Fastqsanger.gz | |||
| SRR1012602.fastq.gz | Fastqsanger.gz | |||
| SRR1012603.fastq.gz | Fastqsanger.gz | |||
| SRR1012598.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Vertebrate limbs develop by integrating signals that control patterning along three main orthogonal axes. Flank-produced retinoic acid (RA) is initially required for limb induction and establishment of the apical ectodermal ridge (AER), a distal signaling center that produces fibroblast growth factors (FGFs), which are essential for limb growth and distalization. Once the AER is established, RA:FGF antagonism determines the restricted expression of a set of genes that control limb proximodistal patterning. Essential for this antagonism is the activation by FGF of the RA-degrading enzyme CYP26B1 in the distal limb bud. In addition, sonic hedgehog produced from the zone of polarizing activity (ZPA) is essential for distal limb anteroposterior patterning and contributes to RA reduction by cooperating in CYP26B1 activation. Meis transcription factors are expressed in the proximal limb bud, are activated by RA and can regulate proximodistal limb development; however, the mechanisms underlying their activity remain unknown. Here we studied Meis function in the mouse limb bud through Meis2 conditional overexpression and elimination of Meis1 and Meis2. We found that Meis activity is first required for limb bud initiation and the proper establishment of the AER and ZPA signaling centers, and subsequently for the development of proximal limb structures. Functional genomic analyses reveal that Meis is an important conveyor of the RA:FGF antagonism through the regulation of components of the RA and FGF signaling pathways, including CYP26B1. In addition, Meis regulates a set of proximal limb genes controlling proximodistal patterning and differentiation. Our work reveals a regulatory module essential for limb patterning and potentially co-opted in other patterning processes involving RA:FGF antagonism.
2018-09-25 | GSE51374 | GEO
Project description:Suppression of Meis genes in the distal limb bud is required for Proximal-Distal (PD) specification of the forelimb. Polycomb group (PcG) factors play a role in downregulation of retinoic acid (RA)-related signals in the distal forelimb bud, causing Meis repression. It is, however, not known if downregulation of RA-related signals and PcG-mediated proximal genes repression are functionally linked. Here, we reveal that PcG factors and RA-related signals antagonize each other to polarize Meis2 expression along the PD axis. With mathematical modeling and simulation, we propose that PcG factors are required to adjust the threshold for RA-related signaling to regulate Meis2 expression. Finally, we show that a variant Polycomb repressive complex 1 (PRC1), incorporating PCGF3 and PCGF5, represses Meis2 expression in the distal limb bud. Taken together, we reveal a previously unknown link between PcG proteins and downregulation of RA-related signals to mediate the phase transition of Meis2 transcriptional status during forelimb patterning.
2018-09-07 | GSE105206 | GEO
Project description:Meis1 and Meis2 are highly similar homeodomain transcription factors that regulate organogenesis through cooperation with Hox proteins. Overexpression experiments have suggested an essential role for Meis factors in limb proximo-distal patterning; however, loss-of-function experiments supporting this notion have not been reported. Meis1 and Meis2 are coexpressed during limb development, first in the lateral plate mesoderm, before limb induction, and then they become restricted to a proximal domain of the growing limb bud. Here, we report that complete double conditional Meis1/2 inactivation in the lateral plate mesoderm leads to limb agenesis. Meis factors cooperate with Tbx factors in this function, extensively co-binding with Tbx to genomic sites and co-regulating enhancers of fgf10, a critical factor in limb initiation. Limbs with three deleted Meis alleles develop a complete PD set of limb skeletal elements, but show proximal-specific skeletal hypoplasia and agenesis of posterior skeletal elements. This failure in posterior skeletal element specification reveals an early role of Meis factors in establishing the limb AP prepattern required for Shh activation at later stages. Our results uncover novel roles for Meis transcription factors in early limb development and identify their involvement in new molecular interaction networks that regulate organogenesis
2020-05-25 | GSE134034 | GEO
Project description:Meis1 and Meis2 are highly similar homeodomain transcription factors that regulate organogenesis through cooperation with Hox proteins. Overexpression experiments have suggested an essential role for Meis factors in limb proximo-distal patterning; however, loss-of-function experiments supporting this notion have not been reported. Meis1 and Meis2 are coexpressed during limb development, first in the lateral plate mesoderm, before limb induction, and then they become restricted to a proximal domain of the growing limb bud. Here, we report that complete double conditional Meis1/2 inactivation in the lateral plate mesoderm leads to limb agenesis. Meis factors cooperate with Tbx factors in this function, extensively co-binding with Tbx to genomic sites and co-regulating enhancers of fgf10, a critical factor in limb initiation. Limbs with three deleted Meis alleles develop a complete PD set of limb skeletal elements, but show proximal-specific skeletal hypoplasia and agenesis of posterior skeletal elements. This failure in posterior skeletal element specification reveals an early role of Meis factors in establishing the limb AP prepattern required for Shh activation at later stages. Our results uncover novel roles for Meis transcription factors in early limb development and identify their involvement in new molecular interaction networks that regulate organogenesis.
2021-03-29 | GSE134039 | GEO
Project description:To investigate the role FGF signaling in limb bud development we inhibited FGF signaling in limb bud explants by treatment with 5µM SU5402, an FGFR inhibitor, or DMSO as control. We then performed mRNA sequencing on RNA collected after 48h of treatment to analyse the effect on gene expression.
2023-08-24 | GSE223444 | GEO
Project description:Vertebrate axial skeletal patterning is controlled by coordinated collinear expression of Hox genes and axial level-dependent activity of Hox protein combinations. Transcription factors of the Meis family act as cofactors of Hox proteins and profusely bind to Hox complex DNA, however their roles in mammalian axial patterning have not been established. Similarly, retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors, however whether this role is related to Meis/Hox regulation or functions in axial patterning remains unknown. Here we study the role of Meis factors in axial skeleton formation and its relationship to the RA pathway by characterizing Meis1, Meis2 and Raldh2 mutant mice. We report that Meis and Raldh2 regulate each other in a positive feedback regulatory loop that controls axial skeletal identity. Meis elimination produces homeotic transformations similar to those found in Raldh2 and anterior-Hox mutants and disrupts the expression of Hox target genes without changing the transcriptional profiles of Hox complexes. We propose that Meis regulates vertebrate axial skeleton patterning by exclusively affecting Hox protein function, and that alterations in RA levels can produce homeotic transformations without altering Hox transcription through regulating Meis expression.
2020-12-22 | GSE146301 | GEO
Project description:This is the simple model without diffusion described in th epublication
Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling.
Goldbeter A, Gonze D, Pourquié O. Dev Dyn. 2007 Jun;236(6):1495-508. PMID:
17497689, doi:10.1016/j.jtbi.2008.01.006
Abstract:
The establishment of thresholds along morphogen gradients in the embryo is poorly understood. Using mathematical modeling, we show that mutually inhibitory gradients can generate and position sharp morphogen thresholds in the embryonic space. Taking vertebrate segmentation as a paradigm, we demonstrate that the antagonistic gradients of retinoic acid (RA) and Fibroblast Growth Factor (FGF) along the presomitic mesoderm (PSM) may lead to the coexistence of two stable steady states. Here, we propose that this bistability is associated with abrupt switches in the levels of FGF and RA signaling, which permit the synchronized activation of segmentation genes, such as mesp2, in successive cohorts of PSM cells in response to the segmentation clock, thereby defining the future segments. Bistability resulting from mutual inhibition of RA and FGF provides a molecular mechanism for the all-or-none transitions assumed in the "clock and wavefront" somitogenesis model. Given that mutually antagonistic signaling gradients are common in development, such bistable switches could represent an important principle underlying embryonic patterning.
Originally created by libAntimony v1.4 (using libSBML 3.4.1)
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000275 | BioModels
Project description:Retinoic acid (RA) functions as a ligand for the nuclear RA receptors (RARs), which regulate the expression of target genes by binding to RA response elements. RA signaling is required for multiple processes during chordate embryonic development, such as body axis extension, hindbrain antero-posterior patterning and forelimb bud initiation. Although some RA target genes have been identified, little is known about the genome-wide effects of RA signaling during in vivo embryonic development. Here we stimulate the RA pathway during development by treating zebrafish embryos with all-trans-RA (atRA), the most abundant form of RA, and use a combination of RNA-seq, ATAC-seq, ChIP-seq and HiChIP to gain insight into the molecular mechanisms by which RA signaling control target gene expression. We find that RA signaling is involved in anterior/posterior patterning and development of the central nervous system, participating in the transition from pluripotency to differentiation. atRA treatment also induces alterations in chromatin accessibility during early development and promotes chromatin binding of RARaa and the RA targets Hoxb1b, Meis2b and Sox3, which cooperate in central nervous system development. Finally, we show that RA induces a rewiring of chromatin architecture, with alterations in chromatin 3D interactions that are consistent with target gene expression. This is illustrated by the specific induction of anterior HoxB genes by RARs, among other examples. Altogether, our findings identify genome-wide targets of RA signaling during embryonic development and provide a molecular mechanism by which developmental signaling pathways regulate the expression of target genes by altering chromatin topology.
2023-06-13 | GSE233689 | GEO
Project description:Retinoic acid (RA) functions as a ligand for the nuclear RA receptors (RARs), which regulate the expression of target genes by binding to RA response elements. RA signaling is required for multiple processes during chordate embryonic development, such as body axis extension, hindbrain antero-posterior patterning and forelimb bud initiation. Although some RA target genes have been identified, little is known about the genome-wide effects of RA signaling during in vivo embryonic development. Here we stimulate the RA pathway during development by treating zebrafish embryos with all-trans-RA (atRA), the most abundant form of RA, and use a combination of RNA-seq, ATAC-seq, ChIP-seq and HiChIP to gain insight into the molecular mechanisms by which RA signaling control target gene expression. We find that RA signaling is involved in anterior/posterior patterning and development of the central nervous system, participating in the transition from pluripotency to differentiation. atRA treatment also induces alterations in chromatin accessibility during early development and promotes chromatin binding of RARaa and the RA targets Hoxb1b, Meis2b and Sox3, which cooperate in central nervous system development. Finally, we show that RA induces a rewiring of chromatin architecture, with alterations in chromatin 3D interactions that are consistent with target gene expression. This is illustrated by the specific induction of anterior HoxB genes by RARs, among other examples. Altogether, our findings identify genome-wide targets of RA signaling during embryonic development and provide a molecular mechanism by which developmental signaling pathways regulate the expression of target genes by altering chromatin topology.
2023-06-13 | GSE233697 | GEO
Project description:Retinoic acid (RA) functions as a ligand for the nuclear RA receptors (RARs), which regulate the expression of target genes by binding to RA response elements. RA signaling is required for multiple processes during chordate embryonic development, such as body axis extension, hindbrain antero-posterior patterning and forelimb bud initiation. Although some RA target genes have been identified, little is known about the genome-wide effects of RA signaling during in vivo embryonic development. Here we stimulate the RA pathway during development by treating zebrafish embryos with all-trans-RA (atRA), the most abundant form of RA, and use a combination of RNA-seq, ATAC-seq, ChIP-seq and HiChIP to gain insight into the molecular mechanisms by which RA signaling control target gene expression. We find that RA signaling is involved in anterior/posterior patterning and development of the central nervous system, participating in the transition from pluripotency to differentiation. atRA treatment also induces alterations in chromatin accessibility during early development and promotes chromatin binding of RARaa and the RA targets Hoxb1b, Meis2b and Sox3, which cooperate in central nervous system development. Finally, we show that RA induces a rewiring of chromatin architecture, with alterations in chromatin 3D interactions that are consistent with target gene expression. This is illustrated by the specific induction of anterior HoxB genes by RARs, among other examples. Altogether, our findings identify genome-wide targets of RA signaling during embryonic development and provide a molecular mechanism by which developmental signaling pathways regulate the expression of target genes by altering chromatin topology.
2023-06-13 | GSE233695 | GEO