Biology subjects

El Bakkali, A.

Publications and source records attributed to El Bakkali, A..

6 recordsLinked to original sources

bioRxiv2025

CDC14 phosphatases control adipogenesis via PPARγ de-phosphorylation

Adipogenesis is a finely tuned process requiring an appropriate balance between proliferation and differentiation. We demonstrate that CDC14, a CDK-counteracting phosphatase, regulates adipogenesis and glucose metabolism in mammals. Simultaneous depletion of CDC14A and CDC14B protects against high-fat diet-induced obesity, hepatic steatosis and glucose intolerance in vivo. Lack of these phosphatases blocks differentiation of stem cells into adipocytes, a defect rescued by the PPAR{gamma} agonist troglitazone. Mechanistically, we show that CDC14 counteracts ERK2 and CDK5-induced phosphorylation of PPAR{gamma}, a master regulator of adipogenesis, by directly dephosphorylating S112, S273 and T296 residues. This study supports the idea that cell cycle regulators in multicellular organisms evolved to coordinate the balance between proliferation and differentiation in different cell types. Furthermore, since PPAR{gamma} is a key target of anti-diabetic drugs and a central regulator of adipogenesis and metabolism, these findings may have important implications for treatment of metabolic diseases such as type 2 diabetes.

cell biology↗

bioRxiv2025

Genomic insights into the local adaptation of spontaneously occurring populations of olive trees (Olea europaea ssp. europaea var. sylvestris) in the Mediterranean Basin

Living organisms are increasingly threatened by significant environmental changes, primarily driven by human-induced global alterations. Understanding and forecasting species adaptive responses to these environmental changes is therefore crucial for enhancing conservation efforts. In the Mediterranean Basin (MB), the average temperature is rising at a rate 20% faster than the global average, placing regional biodiversity at heightened risk. The study of local adaptation is thus particularly relevant. In the western MB, spontaneously occurring olive populations consist of both wild olives and admixed resulting of crop-to-wild gene flow. The wild is likely harbouring adaptive genetic variation shaped by local environmental pressures. In this study, we analysed target genomic sequencing data from spontaneously occurring populations (comprising both wild and admixed trees) as well as cultivated olive trees. We performed selective sweep and GEA analyses in wild olives to identify genomic regions associated with environmental variables. Our findings identified signatures of adaptation particularly associated with precipitation and temperature. Notably, admixed individuals retained many wild candidate SNPs in their genomes suggesting that they might retain a certain level of adaptation to their local environment. Those results are in line with recent studies suggesting hybrids could adapt more rapidly to novel environments than their parental populations. Key-words: Local adaptation, selective sweep detection, crop-to-wild gene flow, Olea europaea L., population genomics, genome-environment association

evolutionary biology↗

bioRxiv2024

Genome-wide association analysis of flowering date in a collection of cultivated olive tree

1.Flowering date in perennial fruit trees is an important trait for fruit production. Depending on the winter and spring temperatures, flowering of olive may be advanced, delayed, or even suppressed. Deciphering the genetic control of flowering date is thus key to help selecting cultivars better adapted to the current climate context. Here, we investigated the genetic determinism of full flowering date stage in cultivated olive based on capture sequencing data of 318 genotypes from the worldwide olive germplasm bank of Marrakech, Morocco. The genetic structure of this collection was organized in three clusters that were broadly attributed to eastern, central, and western Mediterranean regions, based on the presumed origin of genotypes. Flowering dates, collected over seven years, were used to estimate the genotypic best linear unbiased predictors, which were then analyzed in a genome-wide association study. Loci with small effects were significantly associated with the studied trait, by either a single- or a multi-locus approach. The three most robust loci were located on chromosomes 01 and 04, and on a scaffold, and explained 7.1%, 6.2%, and 6.5 % of the trait variance, respectively. A significantly higher accuracy in the best linear unbiased predictors of flowering date prediction was reported with Ridge-compared to LASSO-based genomic prediction model. Along with genomic association results, this suggests a complex polygenic determinism of flowering date, as seen in many other fruit perennials. These results and the screening of associated regions for candidate genes open perspectives for further studies and breeding programs targeting flowering date.

genetics↗

bioRxiv2023

Genomic evidence of genuine wild versus admixed olive populations evolving in the same natural environments in western Mediterranean Basin

Admixtures between wild animals and plants and their domesticated relatives are widely documented. This can have positive or negative impacts on the evolution of admixed populations in natural environments, yet the phenomenon is still misunderstood in long-lived woody species, contrary to short-lived crops. Wild olive Olea europaea L. occurs in the same eco-geographical range as domesticated olive, i.e. the Mediterranean Basin (MB). Moreover, it is an allogamous and anemophilous species whose seeds are disseminated by birds, i.e. factors that drive gene flow between crops and their wild relatives. Here we investigated the genetic structure of western MB wild olive populations in natural environments assuming a homogenous gene pool with limited impact of cultivated alleles, as previously suggested. We used a target sequencing method based on annotated genes from the Farga reference genome to analyze 27 western MB olive tree populations sampled in natural environments in France, Spain and Morocco. We also target sequenced cultivated olive tree accessions from the Worldwide Olive Germplasm Bank of Marrakech and Porquerolles and from an eastern MB wild olive tree population. We combined PCA, sNMF, pairwise Fst and TreeMix and clearly identified genuine wild olive trees throughout their natural distribution range along a north-south gradient including, for the first time, in southern France. However, contrary to our assumption, we highlighted more admixed than genuine wild olive trees. Our results raise questions regarding the admixed population evolution pattern in this environment, which might be facilitated by crop-to-wild gene flow.

evolutionary biology↗

bioRxiv2020

A cell cycle kinase-phosphatase module restrains PI3K-Akt activity in an mTORC1-dependent manner

The AKT-mTOR pathway is a central regulator of cell growth and metabolism. Upon sustained mTOR activity, AKT activity is attenuated by a feedback loop that restrains upstream signaling. However, how cells control the signals that limit AKT activity is not fully understood. Here we show that MASTL/Greatwall, a cell-cycle kinase that supports mitosis by phosphorylating the PP2A/B55 inhibitors ENSA/ARPP19, inhibits PI3K-AKT activity by sustaining mTORC1- and S6K1-dependent phosphorylation of IRS1 and GRB10. Genetic depletion of MASTL results in an inefficient feedback loop and AKT hyperactivity. These defects are rescued by expression of phospho-mimetic ENSA/ARPP19 or inhibition of PP2A/B55 phosphatases. MASTL is directly phosphorylated by mTORC1, thereby limiting the PP2A/B55-dependent dephosphorylation of IRS1 and GRB10 downstream of mTORC1. Downregulation of MASTL results in increased glucose uptake in vitro and increased glucose tolerance in adult mice, suggesting the relevance of the MASTL-PP2A/B55 kinase-phosphatase module in controlling AKT and maintaining metabolic homeostasis.

cell biology↗

bioRxiv2018

Plk1 overexpression suppresses tumor development by inducing chromosomal instability

Polo-like kinase 1 (Plk1) is a protein kinase currently considered as an attractive cancer target due to its critical role in the cell division cycle. Plk1 is overexpressed in a wide spectrum of human tumors, being frequently considered as an oncogene. However, its contribution to tumor development is unclear. Using a new inducible knock-in mouse model we report here that Plk1 overexpression does not favor cell proliferation but rather results in abnormal chromosome segregation and cytokinesis, leading to the formation of polyploid cells with reduced proliferative potential. Mechanistically, these cytokinesis defects correlate with defective loading of Cep55 and ESCRT complexes to the abscission bridge during cytokinesis in a Plk1 kinase-dependent manner. In vivo, elevated levels of Plk1 markedly prevent the development of mammary gland tumors induced either by KrasG12D or Her2, in the presence of increased rates of chromosome instability. In patients, higher Plk1 expression levels are associated with significantly increased overall survival in breast cancer subtypes. These data suggest that, despite the therapeutic benefits of inhibiting Plk1 due to its essential role in tumor cell cycles, Plk1 overexpression has tumor suppressive properties by perturbing mitotic progression and cytokinesis.

cancer biology↗