Biology subjects

Laurin, M.

Publications and source records attributed to Laurin, M..

8 recordsLinked to original sources

bioRxiv2024

ARHGEF3 Regulates Hair Follicle Morphogenesis

During embryogenesis, cells arrange into precise patterns that enable tissues and organs to develop specialized functions. Despite its critical importance, the molecular choreography behind these collective cellular behaviors remains elusive, posing a major challenge in developmental biology and limiting advances in regenerative medicine. By using the mouse hair follicle as a mini-organ system to study the formation of bud-like structures during embryonic development, our work uncovers a crucial role for the Rho GTPase regulator ARHGEF3 in hair follicle morphogenesis. We demonstrate that Arhgef3 expression is upregulated at the onset of hair follicle placode formation. In Arhgef3 knockout animals, we observed defects in placode compaction, leading to impaired hair follicle downgrowth. Through cell culture models, we show that ARHGEF3 promotes F-actin accumulation at the cell cortex and P-cadherin enrichment at cell-cell junctions. Collectively, our study identifies ARHGEF3 as a new regulator of cell shape rearrangements during hair placode morphogenesis, warranting further exploration of its role in other epithelial appendages that arise from similar developmental processes.

developmental biology↗

bioRxiv2024

EPHA1 and EPHB4 tyrosine kinase receptors regulate epithelial morphogenesis

Organ formation and homeostasis require the coordination of cell-cell adhesion, epithelial cell polarity and orientation of cell division to organize epithelial tissue architecture. We have previously identified proximity protein networks acting downstream of members of the EPH family of tyrosine kinase receptors and found within these networks an enrichment of components associated with cell morphogenesis and cell-cell junctions. Here, we show that two EPH receptors, EPHA1 and EPHB4, are localized to the basolateral domain of Caco-2 cells in spheroidal cultures. Depletion of either EPHA1 or EPHB4 disrupts spheroid morphogenesis, without affecting cell polarity, but via randomizing mitotic spindle orientation during cell division. Strikingly, EPHA1 and EPHB4 exert this function independently of their catalytic activity but still requiring EFN ligand binding. Consistent with this, the most abundantly expressed EPHB4 ligand in Caco-2 cells, EFNB2, is also compartmentalized at the basolateral domain in spheroids, and is required for epithelial morphogenesis. Taken together, our data reveal a new role for EPHRs in epithelial morphogenesis.

cell biology↗

bioRxiv2023

The polarity protein Yurt associates with the lateral domain via basic and hydrophobic motifs embedded in its FERM domain

The subcellular distribution of the polarity protein Yrt is subjected to a spatio-temporal regulation in D. melanogaster embryonic epithelia. After cellularization, Yrt binds to the lateral membrane of ectodermal cells and maintains this localization throughout embryogenesis. During terminal differentiation of the epidermis, Yrt accumulates to septate junctions and is also recruited to the apical domain. While the mechanisms through which Yrt associates with septate junctions and the apical domain have been deciphered, how Yrt binds to the lateral membrane remains as an outstanding puzzle. Here, we show that the FERM domain of Yrt is necessary and sufficient for membrane localization. Our data also establish that the FERM domain of Yrt directly binds negatively charged phospholipids. Moreover, we demonstrate that positively charged amino acid motifs embedded within the FERM domain mediates Yrt membrane association. Finally, we provide evidence suggesting that Yrt membrane association is functionally important. Overall, our study highlights the molecular basis of how Yrt associates with the lateral membrane during the developmental time window where it is required for segregation of lateral and apical domains. Summary statement This study reveals how Yurt associates with membrane lipids in epithelial cells, thereby further illuminating the mechanisms sustaining cell polarization and tissue morphogenesis.

cell biology↗

bioRxiv2021

Distributions of extinction times from fossil ages and tree topologies: the example of some mid-Permian synapsid extinctions

Given a phylogenetic tree that includes only extinct, or a mix of extinct and extant taxa, where at least some fossil data are available, we present a method to compute the distribution of the extinction time of a given set of taxa under the Fossilized-Birth-Death model. Our approach differs from the previous ones in that it takes into account (i) the possibility that the taxa or the clade considered may diversify before going extinct and (ii) the whole phylogenetic tree to estimate extinction times, whilst previous methods do not consider the diversification process and deal with each branch independently. Because of this, our method can estimate extinction times of lineages represented by a single fossil, provided that they belong to a clade that includes other fossil occurrences. We assess and compare our new approach with a standard previous one using simulated data. Results show that our method provides more accurate confidence intervals. This new approach is applied to the study of the extinction time of three Permo-Carboniferous synapsid taxa (Ophiacodontidae, Edaphosauridae, and Sphenacodontidae) that are thought to have disappeared toward the end of the Cisuralian (early Permian), or possibly shortly thereafter. The timing of extinctions of these three taxa and of their component lineages supports the idea that the biological crisis in the late Kungurian/early Roadian consisted of a progressive decline in biodiversity throughout the Kungurian.

evolutionary biology↗

bioRxiv2019

The Relationship Between Genome Size and Metabolic Rate in Extant Vertebrates

Genome size has long been hypothesized to affect metabolic rate in various groups of animals. The mechanism behind this proposed association is the nucleotypic effect, in which large nucleus and cell sizes influence cellular metabolism through surface area-to-volume ratios. Here, we provide a review of the recent literature on the relationship between genome size and metabolic rate. We also conduct an analysis using phylogenetic comparative methods and a large sample of extant vertebrates. We find no evidence that the effect of genome size improves upon models in explaining metabolic rate variation. Not surprisingly, our results show a strong positive relationship between metabolic rate and body mass, as well as a substantial difference in metabolic rate between endothermic and ectothermic vertebrates, controlling for body mass. The presence of endothermy can also explain elevated rate shifts in metabolic rate whereas genome size cannot. We further find no evidence for a punctuated model of evolution for metabolic rate. Our results do not rule out the possibility that genome size affects cellular physiology in some tissues, but they are consistent with previous research suggesting little support for a direct functional connection between genome size and basal metabolic rate in extant vertebrates.

evolutionary biology↗

bioRxiv2018

Exact distribution of divergence times from fossil ages and tree topologies

Being given a phylogenetic tree of both extant and extinct taxa in which the fossil ages are the only temporal information (namely, in which divergence times are considered unknown), we provide a method to compute the exact probability distribution of any divergence time of the tree with regard to any speciation (cladogenesis), extinction and fossilization rates under the Fossilized-Birth-Death model. We use this new method to obtain a probability distribution for the age of Amniota (the synapsid/sauropsid or bird/mammal divergence), one of the most-frequently used dating constraints. Our results suggest an older age (between about 322 and 340 Ma) than has been assumed by most studies that have used this constraint (which typically assumed a best estimate around 310-315 Ma) and provide, for the first time, a method to compute the shape of the probability density for this divergence time.

evolutionary biology↗

bioRxiv2018

A Reassessment of the Taxonomic Position of Mesosaurs Based on Two Data Matrices

1The Early Permian mesosaurs are the oldest known primarily aquatic amniotes. Despite the interest that they have generated over time, their affinities remain controversial. Recently, two hypotheses have been supported, in which mesosaurs are either the sister-group of all other sauropsids, or the sister-group of other parareptiles. We recently upheld the former hypothesis, but in the latest study on mesosaur affinities, MacDougall et al. published a study highly critical of our work, while upholding the hypothesis that mesosaurs are basal parareptiles. We expect that the debate about mesosaur affinities will continue in the foreseeable future, but we wish to respond to the two central comments published by MacDougall et al. in 2018, who argue that variability in the temporal fenestration of early sauropsids, combined with the omission of several recently-described parareptile taxa, explain the differences in topologies between their study and ours. Reanalyzing our data matrix and theirs without characters linked with temporal fenestration, and removing from their matrix the parareptile taxa that they added (and that we omitted) does not alter the resulting topologies. Thus, their main conclusions are false; the differences in taxonomic position of mesosaurs must result from character choice and scoring differences.

paleontology↗

bioRxiv2018

What do ossification sequences tell us about the origin of extant amphibians?

ABSTRACTThe controversial origin of extant amphibians has been studied using several sources of data and methods, including phylogenetic analyses of morphological data, molecular dating, stratigraphic data, and integration of ossification sequence data, but a consensus has failed to emerge. We have compiled five datasets to assess the relative support for six competing hypotheses about the origin of extant amphibians: a monophyletic origin among temnospondyls, a monophyletic origin among lepospondyls, a diphyletic origin among both temnospondyls and lepospondyls, a diphyletic origin among temnospondyls alone, and two variants of a triphyletic origin, in which anurans and urodeles come from different temnospondyl taxa while caecilians come from lepospondyls and are either closer to anurans and urodeles or to amniotes. Our datasets comprise ossification sequences of up to 107 terminal taxa and up to eight cranial bones, and up to 65 terminal taxa and up to seven appendicular bones, respectively. Among extinct taxa, only two or three temnospondyl can be analyzed simultaneously for cranial data, but this is not an insuperable problem because each of the six tested hypotheses implies a different position of temnospondyls and caecilians relative to other sampled taxa. For appendicular data, more extinct taxa can be analyzed, including some lepospondyls and the finned tetrapodomorph Eusthenopteron, in addition to temnospondyls. The data are analyzed through maximum likelihood, and the AICc (corrected Akaike Information Criterion) weights of the six hypotheses allow us to assess their relative support. By an unexpectedly large margin, our analyses of the cranial data support a monophyletic origin among lepospondyls; a monophyletic origin among temnospondyls, the current near-consensus, is a distant second. All other hypotheses are exceedingly unlikely according to our data. Surprisingly, analysis of the appendicular data supports triphyly of extant amphibians within a clade that unites lepospondyls and temnospondyls, contrary to all molecular and recent paleontological phylogenies, but this conclusion is not very robust.View Full Text

paleontology↗