Axolotl mandible regeneration occurs through mechanical gap closure and a shared regenerative program with the limb
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1129508 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The mandible plays an essential part in human life and, thus, defects in this structure can dramatically impair the quality of life in patients. Axolotls, unlike humans, are capable of regenerating their lower jaws; however, the underlying mechanisms and their similarity to those in limb regeneration are unknown. In this work, we used morphological, histological, and transcriptomic approaches to analyze the regeneration of lateral resection defects in the axolotl mandible. We found that this structure can regenerate all missing tissues in 90 days through gap minimization, blastema formation, and finally tissue growth, differentiation, and integration. Moreover, transcriptomic comparisons of regenerating mandibles and limbs showed that they share molecular phases of regeneration, that these similarities peak during blastema stages, and that mandible regeneration occurs at a slower pacing. Altogether, our study demonstrates the existence of a shared regenerative program used in two different regenerating body structures with different embryonic origins in the axolotl, and contributes to our understanding of the minimum requirements for a successful regeneration in vertebrates, bringing us closer to understand similar lesions in human mandibles.
2024-08-29 | GSE271056 | GEO
Project description:Human diseases like oral cancer or injuries may cause irreversible substantial jaw defects. Axolotls are of special interest in regenerative maxillofacial research due to their unique ability to completely renew amputated jaws. Here we performed differential gene expression analyses based on RNA-seq for regenerating jaw tissue of the Mexican axolotl (Ambystoma mexicanum) to identify key players in this regenerative process. Within differentially expressed genes (p<0.001) we use enrichment and network analyses to identify increased expression of structural components crucial for tissue repair (Thbs3, Thbs4 and Col3a1) as well as for extracellular matrix structure (further collagens and Matn4). Genes of enzymatic function (AldoA, AldoC, Eno1, Ckm and Ak6) as well as muscle components (Atp2A1, Pvalb, Tpm3) are down-regulated. This first RNA-seq study on axolotl jaw tissue can help to elucidate the general molecular mechanisms underlying mandible regeneration and offer a chance for new regenerative strategies focusing on morphologically and functionally adequate replacement of these complex tissues.
2018-12-01 | GSE95355 | GEO
Project description:In order to understand the genomic and transcriptomic variability of the axolotl pallium, as well as reconstruct their intrinsic gene regulatory networks, we performed single-nucleus multiome sequencing (RNA and open chromatin) of whole axolotl pallium.
2022-07-20 | E-MTAB-11666 | biostudies-arrayexpress
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:To investigate spatial heterogeneities in the axolotl forebrain, a coronal section of it was obtained for spatial transcriptomics using Visium V1.
2022-07-20 | E-MTAB-11665 | biostudies-arrayexpress
Project description:Identifying the genetic program that induces limb regeneration in salamanders is an important resource for regenerative medicine, which currently lacks tools to promote regeneration of functional body structures. The genetic network underlying limb regeneration has been elusive due to the complexity of the injury response that occurs concomitant to blastema formation. Here we performed parallel expression profile time courses of non-regenerative lateral wounds versus amputated limbs in axolotl. We show that limb regeneration occurs in three distinguishable phases--early wound healing followed by a transition phase leading to establishment of the limb development program. By focusing on the transition phase, we identified 93 strictly regeneration-associated genes involved in oxidative stress response, chromatin modification, epithelial development and limb development. The specific expression of the genes was confirmed by in situ hybridization. Regeneration-specific expression databases are critical resources for understanding how regeneration-relevant phenotypes can be induced from adult cells Regeneration of the axolotl forelimb lower arm was compared with the healing of a deep lateral injury in a high density timecourse (uncut, 3h, 6h, 9h, 12h, 24h, 36h, 52h, 72h, 120h, 168h, 288h and 528h after injury). Three independent biological replicates were performed using separate cluches of animals. Amputated and lateral wound samples were made as matched contralateral samples of four pooled animals per timepoint.
2013-01-01 | E-GEOD-36451 | biostudies-arrayexpress
Project description:Previous analysis of Myf5-/-:MyoD-/- mouse fetuses lacking skeletal muscle demonstrated the importance of muscle contraction and static loading in mouse skeletogenesis. Previous analysis of Myf5-/-:MyoD-/- mouse fetuses lacking skeletal muscle demonstrated the importance of muscle contraction and static loading in mouse skeletogenesis. Among abnormal skeletal features, micrognathia (mandibular hypoplasia) was detected: small, bent and posteriorly displaced mandible. As an example of Waddingtonian epigenetics, we suggest that muscle, in addition to acting via mechanochemical signal transduction pathways, networks and promoters, also exerts secretory stimuli on skeleton. Our goal is to identify candidate molecules at that muscle-mandible interface. By employing Systematic Subtractive Microarray Analysis approach, we compared gene expression between mandibles of amyogenic and wild type mouse fetuses. We identified a set of candidate genes with involvement in mandibulardevelopment: Cacna1s, Ckm, Des, Mir300, Myog and Tnnc1. We also performed mouse-to-human translational experiments and found analogies. In the light of our findings we discuss various players in mandibular morphogenesis and make an argument for the need to consider mandibular development as a consequence of reciprocal epigenetic interactions of both skeletal and non-skeletal compartments.
2018-01-30 | GSE109779 | GEO