Identifying an Apical Ectodermal Ridge (AER) signature in embryonic day 11.5 mouse forelimb.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE51877 | GEO | 2013/11/15
SECONDARY ACCESSION(S): PRJNA225645
REPOSITORIES: GEO
Similar Datasets
Project description:The apical ectodermal ridge (AER) is a transient ectodermal population of cells that defines the dorso-ventral border of the developing limb bud. It functions as a major signaling centre that, through the secretion of various growth factors including FGF8, instructs the growth and patterning of the developing limb. We have identified that the AER expresses markers of cellular senescence and wanted to examine if there was any overlap with oncogene-induced senescence, an adult form of senescence induced in premalignant lesions. To achieve this, we microdissected the AER from embryonic day 11.5 mouse embryos. In addition, we collected the surface ectoderm from the proximal limb bud, that was not senescent and profiled both populations, to identify those genes that are enriched in the AER The AER was microdissected from embryonic day 11.5 mouse forelimb. Surface ectoderm from the posterior limb was used as a comparative control. Samples from 2-3 mice were pooled for each replicate, for 3-4 replicates.
2013-11-15 | E-GEOD-51877 | biostudies-arrayexpress
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:Humans and other tetrapods are considered to require apical-ectodermal-ridge, AER, cells for limb development, and AER-like cells are suggested to be re-formed to initiate limb regeneration. Paradoxically, the presence of AER in the axolotl, the primary regeneration model organism, remains controversial. Here, by leveraging a single-cell transcriptomics-based multi-species atlas, composed of axolotl, human, mouse, chicken, and frog cells, we first established that axolotls contain cells with AER characteristics. Surprisingly, further analyses and spatial transcriptomics revealed that axolotl limbs do not fully re-form AER cells during regeneration. Moreover, the axolotl mesoderm displays part of the AER machinery, revealing a novel program for limb (re)growth. These results clarify the debate about the axolotl AER and the extent to which the limb developmental program is recapitulated during regeneration.
2023-09-20 | GSE243225 | GEO
Project description:Purpose: The response to Hedgehog signaling in the limb is driven by GLI bound enhancers and the majority of Hh targets in the developing limb bud are regulated solely by the activity of GLI-repressor. Currently we do not have a comprehensive understanding of how GLI bound enhancers respond Hedgehog signaling. The goal of this study is to identify how GLI bound enhancers are regulated by Hedgehog signaling and specifically by GLI-repressor. Methods: ChIP-seq was performed in Embryonic day 10.5 mouse limb buds from mice with endogenously FLAG tagged Gli3. Results: We identified 7282 GLI3 binding regions in the E10.5 limb bud.
2020-01-21 | GSE133710 | GEO
Project description:During limb development, fibroblast growth factors (FGFs) govern proximal-distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal-distal and anterior-posterior axes by maintaining sonic hedgehog (SHH) expression in cells of the zone of polarizing activity (ZPA) in the distal posterior mesoderm. SHH, in turn, maintains FGFs in the apical ectodermal ridge (AER) which caps the distal tip of the limb bud. Crosstalk between FGF and SHH signaling is critical for patterned limb development, but the mechanisms underlying this feedback loop are not well characterized. Implantation of FGF beads in the proximal posterior limb bud can maintain SHH expression in the former ZPA domain (evident 3hrs after application), while prolonged exposure (24hrs) can induce SHH outside of this domain. Although temporally and spatially disparate, comparative analysis of transcriptome data from these different populations enriched molecules required for FGF-mediated SHH regulation.
2018-12-18 | GSE114661 | GEO
Project description:Vertebrate Hox genes are key players in the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that the HoxC gene cluster was globally co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of the HoxC cluster led to mice lacking nails (anonychia) and also hairs (alopecia), a condition stronger than the previously reported loss of function of Hoxc13, which is causative of the ectodermal dysplasia 9 (ECTD9) syndrome in human patients. We further identified, in mammals only, two ectodermal-specific enhancers located upstream the gene cluster, which act synergistically to regulate Hoxc genes in these ectodermal organs. Deletion of these enhancers alone or in combination revealed a strong quantitative component in the regulation of these genes in the ectoderm, suggesting that these two enhancers may have evolved along with mammals to provide the level of HOXC proteins necessary for the full development of hairs and nails.
2020-10-05 | GSE150701 | GEO
Project description:Vertebrate Hox genes are key players in the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that the HoxC gene cluster was globally co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of the HoxC cluster led to mice lacking nails (anonychia) and also hairs (alopecia), a condition stronger than the previously reported loss of function of Hoxc13, which is causative of the ectodermal dysplasia 9 (ECTD9) syndrome in human patients. We further identified, in mammals only, two ectodermal-specific enhancers located upstream the gene cluster, which act synergistically to regulate Hoxc genes in these ectodermal organs. Deletion of these enhancers alone or in combination revealed a strong quantitative component in the regulation of these genes in the ectoderm, suggesting that these two enhancers may have evolved along with mammals to provide the level of HOXC proteins necessary for the full development of hairs and nails.
2020-10-05 | GSE150700 | GEO
Project description:During embryonic development, fields of progenitor cells form complex spatial structures through dynamic interactions with external signaling molecules. However, how complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. For instance several critical signals have been well characterized in the early limb bud, including Sonic hedgehog (Shh) and Fibroblast growth Factor 8 (Fgf8). While the former is expressed in the distal posterior mesenchyme where it acts as the mediator of anterior to posterior (AP) patterning, the latter is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud and directs the outgrowth and the proximal to distal (PD) organization of the limb. Here we use cultured limb mesenchyme cells to try and assess the response of the target Hoxd genes to these two factors. We find that they act synergistically and that both factors are required to get activation of Hoxd13 in limb mesenchymal cells. However, the analysis of the enhancer landscapes flanking the HoxD cluster reveals that the bimodal regulatory switch observed in vivo is not fully achieved under these in vitro conditions, suggesting the requirement for other factors.
2017-03-06 | GSE92556 | GEO
Project description:During embryonic development, fields of progenitor cells form complex spatial structures through dynamic interactions with external signaling molecules. However, how complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. For instance several critical signals have been well characterized in the early limb bud, including Sonic hedgehog (Shh) and Fibroblast growth Factor 8 (Fgf8). While the former is expressed in the distal posterior mesenchyme where it acts as the mediator of anterior to posterior (AP) patterning, the latter is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud and directs the outgrowth and the proximal to distal (PD) organization of the limb. Here we use cultured limb mesenchyme cells to try and assess the response of the target Hoxd genes to these two factors. We find that they act synergistically and that both factors are required to get activation of Hoxd13 in limb mesenchymal cells. However, the analysis of the enhancer landscapes flanking the HoxD cluster reveals that the bimodal regulatory switch observed in vivo is not fully achieved under these in vitro conditions, suggesting the requirement for other factors.
2017-03-06 | GSE92555 | GEO
Project description:Transcriptomes of mouse embryonic autopods were generated detecting expression of approximately 26179 transcripts in the developing forelimb or hindlimb autopods, representing about 58 % of the probe sets on MOE-430 A/B GeneChip. Three biological replicate array experiments were finished for each condition and MAS5.0 signal were used to do data analysis. Forty-four transcripts with expression differences higher than 2-fold were detected(T test, P<0.05), including Tbx4, Tbx5, Hoxc10 and Pitx1 which were previously shown to be differentially expressed in developing forelimb and hindlimb bud by in situ hybridization and SAGE study (Margulies 2001). RTPCR and in situ experiments confirmed several top differentially expressed genes which were newly discovered by our experiments. Vast amount of transcripts and its family members such as Bmp, Fgf, Epha, Wnt, T-box and Hox families detected to be highly expressed or differentially expressed in developing autopods, suggesting that the complexity of transcriptomes of developing autopods and dynamic differential expression and differential combinations of gene expression signals in the developing limb tissue contributes to differences in forelimb versus hindlimb patterning. The differentially expressed genes are the essential factors for morphological diversification of developing limb structures. Keywords = microarray Keywords = mouse Keywords = autopod Keywords = limb Keywords = development Keywords = gene expression Keywords = transcriptome Keywords: repeat sample
2005-06-01 | GSE2560 | GEO