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Retinoic acid receptors and the control of positional information in the regenerating axolotl limb

ABSTRACT: Retinoic acid receptors and the control of positional information in the regenerating axolotl limb

PROVIDER: PRJNA755711 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15505801_1.fastq.gz	Fastqsanger.gz
	SRR15505801_2.fastq.gz	Fastqsanger.gz
	SRR15505802_1.fastq.gz	Fastqsanger.gz
	SRR15505802_2.fastq.gz	Fastqsanger.gz
	SRR15505803_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Retinoic acid receptors and the control of positional information in the regenerating axolotl limb

Project description:We know little about the control of positional information (PI) during axolotl limb regeneration which ensures that the limb regenerates exactly what was amputated and the work reported here investigates this phenomenon. Retinoic acid administration changes the PI in a proximal direction so that a complete limb can be regenerated from a hand. Rather that identifying all the genes altered by RA treatment of the limb, we have eliminated many off-target effects by using retinoic acid receptor selective agonists. We firstly identify the receptor involved in this respecification process as RARα and secondly identify the genes involved by RNA sequencing of the RARα-treated blastemal mesenchyme. We find 1177 up-regulated genes and 1403 down-regulated genes which could be identified using the axolotl genome. These include several genes known to be involved in retinoic acid metabolism and in patterning. Since positional in-formation is thought to be a property of the cell surface of blastemal cells when we examine our dataset with an emphasis on this aspect, we find the top canonical pathway is integrin signaling. In the extracellular matrix compartment, we find an MMP and several collagens are up-regulated and several cell membrane genes and secretory factors are also up-regulated. This provides data for future testing of the function of these candidates in the control of PI during limb regeneration.

2021-08-20 | GSE182296 | GEO

Retinoic acid breakdown is required for proximodistal positional identity during axolotl limb regeneration

Project description:Regenerating limbs retain their proximodistal (PD) positional identity following amputation. This positional identity is encoded genetically by PD patterning genes, which instruct blastema cells to regenerate the appropriate PD limb segment. Retinoic acid (RA) is known to specify proximal limb identity, but how RA concentration is established in the blastema is unknown. Here, we show that RA breakdown via CYP26B1 is essential for determining the RA concentration within blastemas. CYP26B1 inhibition molecularly reprograms distal blastemas into a proximal identity, phenocopying the effects of administering excess RA. We identify Shox as an RA responsive gene that is differentially expressed between proximally and distally amputated blastemas. Ablation of Shox results in shortened limbs with proximal skeletal elements that fail to undergo endochondral ossification. These results suggest that PD positional identity is determined by RA degradation and that targets of RA have a critical role in skeletal element formation during limb regeneration.

2024-07-22 | GSE272731 | GEO

Single-cell level transcriptomic anaylsis of the homeostatic and regenerating axolotl limb

Project description:Regeneration of complex multi-tissue structures, such as limbs, requires the coordinated effort of multiple cell types. In axolotl limb regeneration, the wound epidermis and blastema have been extensively studied via histology, grafting, and bulk-tissue RNA-sequencing. However, studying the contributions of these tissues is hindered due to limited information regarding the molecular identity of the cell types in regenerating limbs. By performing unbiased single-cell RNA-sequencing on over 25,000 cells from axolotl limbs, we identify a plethora of cellular diversity within epidermal, mesenchymal, and hematopoietic lineages in homeostatic and regenerating limbs. We identify regeneration-induced genes, develop putative trajectories for blastema cell differentiation, and propose the molecular identity and origin of fibroblast-derived blastema progenitor cells residing in homeostatic limbs. This work will enable application of molecular techniques to assess the contribution of these populations to limb regeneration. It will also facilitate work aimed at identifying transcripts and cells critical for limb regeneration.

2018-10-25 | GSE121737 | GEO

Retinoic acid breakdown is required for proximodistal positional identity during axolotl limb regeneration

Project description:Retinoic acid breakdown is required for proximodistal positional identity during axolotl limb regeneration

| PRJNA1138466 | ENA

Positional information is reprogrammed in blastema cells of the regenerating limb of the axolotl (Ambystoma mexicanum).

Project description:The regenerating region of an amputated salamander limb, known as the blastema, has the amazing capacity to replace exactly the missing structures. By grafting cells from different stages and regions of blastemas induced to form on donor animals expressing Green Fluorescent Protein (GFP), to non-GFP host animals, we have determined that the cells from early stage blastemas, as well as cells at the tip of late stage blastemas are developmentally labile such that their positional identity is reprogrammed by interactions with more proximal cells with stable positional information. In contrast, cells from the adjacent, more proximal stump tissues as well as the basal region of late bud blastemas are positionally stable, and thus form ectopic limb structures when grafted. Finally, we have found that a nerve is required to maintain the blastema cells in a positionally labile state, thus indicating a role for reprogramming cues in the blastema microenvironment.

| S-EPMC3785456 | biostudies-literature

Regenerating axolotl retinas regrow diverse cell types with modulation by Notch signaling and reconnect to the brain

Project description:We examined uninjured and regenerating axolotl salamander retinas, including their transcriptional profile. We report that at 27 days after a retinectomy (early-mid regeneration), regenerating axolotl retinas exhibit downregulation of genes associated with neuronal networks but upregulation of genes associated with angiogenesis and the extracellular matrix. We also report differential expression of two Notch pathway effector genes, Hes1 and Hes5.

2022-04-10 | GSE200423 | GEO

Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration.

Project description:Injury is a common occurrence in the life of most if not all organisms. Because injury and the extent of damage inflicted are not predictable events, pre-existing tissues must somehow determine how much tissue needs to be restored. It has been known for over a century that amputation position along a proximal-distal (P/D) axis determines the regeneration speed of amputated limbs in regeneration-competent animals1. Yet, it is not clear how an injured limb conveys positional information during regeneration to faithfully restore pre-existing morphologies and functions. Here, we profiled millimetric caudal fins regenerating proximal and distal amputations in the African killifish (Nothobranchius furzeri). We report position-specific, differential modulation of the spatial distribution, duration, and magnitude of proliferation, and the possibility to predict blastema sizes. Regenerating fins profiled by single cell RNA sequencing identified a Transient Regeneration-Activated Cell State (TRACS) enriched in extracellular matrix (ECM) components and modifiers that is proportionally amplified to match a given amputation position. We located this transient cell state to the basal epidermis by gene expression and confocal microscopy, and propose a role for these cells in transducing positional information to the regeneration blastema. Understanding the temporal deployment of regenerative cell states may hold the key to set up a successful regeneration event in organisms with limited regenerative abilities such as humans.

2024-04-01 | GSE260629 | GEO

Single-cell level transcriptomic anaylsis of the homeostatic and regenerating axolotl limb

Project description:Single-cell level transcriptomic anaylsis of the homeostatic and regenerating axolotl limb

| PRJNA498286 | ENA

Gene Expression During the First 28 Days of Axolotl Limb Regeneration

Project description:Here we report the results of a robust microarray experiment that examined the first 28 days of axolotl forelimb regeneration. At each of 20 post-amputation time points, we estimated gene expression for 10 replicate RNA samples that were isolated from 1m of heterogeneous tissue collected from the distal limb tip. The distal 1.0mm of heterogeneous tissue from regenerating limb tip were removed and used for RNA extraction. 10 samples were collected for each of 20 time points.

2015-04-20 | E-GEOD-67118 | biostudies-arrayexpress

Chromatin states at homeoprotein loci distinguish axolotl limb segments prior to regeneration [RNA-seq]

Project description:The salamander limb regenerates only the missing portion. Each limb segment can only form segments equivalent to- or more distal to their own identity, relying on a property termed “positional information”. How positional information is encoded in limb cells has been unknown. By cell-type-specific chromatin profiling of upper arm, lower arm, and hand, we found segment-specific levels of histone H3K27me3 at limb homeoprotein gene loci but not their upstream regulators, constituting an intrinsic segment information code. During regeneration, regeneration-specific regulatory elements became active prior to the re-appearance of developmental regulatory elements. This means that, in the hand segment, the permissive chromatin state of the hand homeoprotein gene HoxA13 engages with regeneration regulatory elements, bypassing the upper limb program. We performed Differential Gene expression analysis using data obtained from RNA-seq of two mature limb segments (mature arm vs hand). Therefore, we performed libraries from the mature arm and 5, 9, 13 dpa regenerating arm blastema.

2023-04-10 | GSE217593 | GEO

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