Biology subjects

Garcia-Garcia, D.

Publications and source records attributed to Garcia-Garcia, D..

7 recordsLinked to original sources

bioRxiv2025

The essential role of connective-tissue cells during axolotl limb regeneration

Axolotls (Ambystoma mexicanum) are known for their remarkable limb-regeneration abilities, which involve the formation of the blastema, a specialized structure consisting of progenitor cells contributed by all major tissues of the limb. Lateral plate mesoderm (LPM)-derived connective tissue (CT) cells dedifferentiate and play a critical role in blastema formation and subsequent limb regeneration. However, the complexity of the blastemas cellular composition and the extent of CT participation and necessity have not been rigorously explored. To address this gap, we conducted spatial transcriptomics using a select array of probes, revealing that CT cells constitute up to 75% of the blastema cells at their peak. Genetic ablation of CT cells significantly delays or truncates limb regeneration, underscoring their necessity during this process. Finally, we analyzed the molecular profile of CT cells throughout the stages of blastema formation and made it accessible through an interactive web platform. Our work reaffirms the central role of CT cells in axolotl limb regeneration and lays the foundation for identifying molecular mechanisms that govern blastema formation during the initial phases of limb regeneration.

developmental biology↗

bioRxiv2024

Modelling the invasion, management strategies and economic impact of the invasive alien aquatic plant Egeria densa

Egeria densa is a south American aquatic plant considered as an invasive alien species with a very aggressive and expansionist behaviour out of its native ecosystems. The widespread decorative use of E. densa in aquariums, coupled with the potential for subsequent disposal malpractice, has resulted in its introduction into a range of vulnerable ecosystems across the globe. This work presents a dynamic model of a population of E. densa based on its accidental introduction into an ecosystem in southeastern Spain. The model allows the simulation of colonisation process and management and disposal strategies. The model considers the influence of environmental variables such as temperature, light and water turbidity on the growth of the species. Among the management strategies tested, the optimal appears to be those of a preventive nature before the plant spreads, given that the costs of removal will be very high at that stage, and with high ecological impacts.

ecology↗

bioRxiv2024

Integrating complexity in population modelling: from matrix to dynamic models using the jellyfish Carybdea marsupialis

Matrix models are widely used in population ecology studies and are valuable for analysing population dynamics. Nonetheless, this approach is somewhat rigid in terms of generating complex scenarios. Starting from the values of the transition matrix, we can build a dynamic model to incorporate more biological-based reality into the model (e.g. polyp stage) and provide a higher flexibility in generating scenarios. As an example, we used the transition matrix calculated for a time series data of a population of the box jellyfish Carybdea marsupialis (L. 1758) in the Western Mediterranean in a previously published study. Dynamic models can help us to better understand the complex relationships that drive populations, test different hypotheses and compare scenarios. The dynamic model was developed in STELLA Architect, calibrated and optimised and it has been used to simulate various scenarios of ecological interest, including a decline in food supply, jellyfish removal strategies, changes in drift currents and changes in substrate availability for planulae to settle. A sensitivity analysis showed that polyp strobilation rate and strobilation pattern were two of the most sensitive variables. This matrix-to-dynamic model approach could be useful to integrate more biological complexity into population models and, in turn, obtain a better fit to the field data.

ecology↗

bioRxiv2024

SRCompiler: Translating Stella dynamic models to open-source R scripts

Stella Architect (iSee Systems) offers an object-oriented environment that facilitates the development of dynamic models. Stella, however, does not support some of the advanced mathematical tools that can be found in mathematical software such as R. Moreover, R is open source, contains numerous libraries and resources, and is used by a large community. However, building dynamic systems, which typically use a large number of differential or difference equations, are more difficult to build in R. To take advantage of both Stella and R, we have developed the SRCompiler (Stella-R Compiler), which is a translator that exports models built in Stella into R scripts. In 2012, a translator from Stella to R was developed based on plain text treatment for Stella, but it had some limitations such as scalability and error handling. Nevertheless, our approach is more versatile, scalable and expandable since it is based on compiler design, defines a formal language, and uses the latest Stella version (v. Architect).In this paper, a classical predator-prey model has been modelled in Stella to show an applied example. Following the translation of the Stella model into R, all the parameters of the model (6 in total) have been optimised to fit model output to the Hudson Bay Companys hare-lynx time series hunting data (1847-1935). Software availabilityO_LIName of software: SRCompiler C_LIO_LISRCompiler Developers: Pastor Hector.M, Morales Enrique C_LIO_LIWeb page: https://github.com/hmpp91/SRCompiler C_LIO_LIAvailable: 2021 C_LIO_LIProgram language: C++ C_LIO_LIProgram size: 197 KB C_LIO_LIAvailability and cost: Open source C_LI

ecology↗

bioRxiv2022

Sexually dimorphic activation of innate antitumour immunity prevents adrenocortical carcinoma development

In contrast with most cancers, adrenocortical carcinomas (ACC) are more frequent in women than men, but the underlying mechanisms of this sexual dimorphism remain elusive. Homozygous deletion of the negative WNT pathway regulator ZNRF3 is the most frequent alteration in ACC patients. Here, we show that Cre-mediated inactivation of Znrf3 in steroidogenic cells of the mouse adrenal cortex is associated with sexually dimorphic tumour progression. Indeed, although most knockout female mice develop metastatic carcinomas over an 18 month-time course, adrenal hyperplasia gradually regresses in male knockout mice. This male-specific regression is associated with induction of senescence and recruitment of macrophages, which differentiate as active phagocytes that clear-out senescent preneoplastic cells. Macrophage recruitment is also observed in female mice. However, it is delayed and dampened compared to males, which allows for tumour progression. Interestingly, testosterone treatment of female knockouts is sufficient to induce senescence, recruitment of phagocytic macrophages and regression of hyperplasia. We further show that although macrophages are present within adrenal tumours at 18 months, MERTKhigh active phagocytes are mostly found in indolent lesions in males but not in aggressive tumours in females. Consistent with our observations in mice, analysis of RNA sequencing data from the TCGA cohort of ACC shows that phagocytic macrophages are more prominent in men than women and associated with better prognosis. Altogether, these data establish that phagocytic macrophages prevent aggressive ACC development in male mice and suggest that they may play a key role in the unusual sexual dimorphism of ACC in patients.

cancer biology↗

bioRxiv2020

Yap haploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy

Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Muller glia. We first discovered an unexpected temporal dynamic of gene compensation. At post-natal stages, Taz upregulation occurs, leading to a gain of function-like phenotype characterized by EGFR signalling potentiation and delayed cell cycle exit of retinal progenitors. In contrast, Yap+/- adult retinas no longer exhibit TAZ-dependent dosage compensation. In this context, Yap haploinsufficiency in aged individuals results in Muller glia dysfunction, late-onset cone degeneration and reduced cone-mediated visual response. Alteration of glial homeostasis and altered patterns of cone opsins were also observed in Muller cell specific conditional Yap knockout mice. Together, this study highlights a novel YAP function in Muller cells for the maintenance of retinal tissue homeostasis and the preservation of cone integrity. It also suggests that YAP haploinsufficiency should be considered and explored as a cause of cone dystrophies in human. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/953943v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@166de41org.highwire.dtl.DTLVardef@898b74org.highwire.dtl.DTLVardef@22ad92org.highwire.dtl.DTLVardef@b189dc_HPS_FORMAT_FIGEXP M_FIG C_FIG Main Points O_LIThis study finds unsuspected dynamics of YAP compensatory mechanisms in the retina of Yap+/- mice C_LIO_LIYap haploinsufficiency results in Muller glia dysfunction in aged mice, leading to late-onset cone dystrophy C_LI

neuroscience↗

bioRxiv2018

Linking YAP to Müller glia quiescence exit in the degenerative retina

Contrasting with fish or amphibian, retinal regeneration from Muller glial cells is largely limited in mammals. In our quest towards the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP, which we previously found to be upregulated in Muller cells following retinal injury. We report that conditional Yap deletion in Muller cells prevents the upregulation of cell cycle genes that normally accompanies reactive gliosis upon photoreceptor cell death. This occurs as a consequence of defective EGFR signaling. Consistent with a function of YAP in triggering Muller glia cell cycle re-entry, we further show that in Xenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. Finally, and noteworthy, we reveal that YAP overactivation in mouse Muller cells is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Muller cell response to injury and highlight a novel YAP-EGFR axis by which Muller cells exit their quiescence state, a critical step towards regeneration.

developmental biology↗