Biology subjects

Pinheiro, D.

Publications and source records attributed to Pinheiro, D..

4 recordsLinked to original sources

bioRxiv2026

Differential turnover of apicobasal regulators drives emergent mechano-response and shape homeostasis

Epithelial cell shape plays a fundamental role in tissue dynamics. Numerous studies have established how cells drastically change their shape to promote epithelial tissue morphogenesis. However, the mechanisms enabling cells to maintain their shape remain far less understood. Here, leveraging live imaging in Drosophila epithelial tissue and theoretical modeling, we identify an emergent mechano-chemical feedback that ensures junction length and cell shape stability, without requiring a dedicated molecular force sensor. We find that an increase in junction length is associated with a passive dilution of E-Cadherin, followed by an increase in Myosin-II-dependent contractility that reduces junction length. Theoretically, we show that this regulation of junction length generically emerges when negative and positive regulators of contractility have distinct kinetics. Experiments confirm that E-Cadherin acts as a negative regulator with slow turnover. Mechanistically, local dilution of E-Cadherin passively lifts an inhibition on lateral apicobasal polarity components, allowing the RhoGEF Cyst -- with its fast turnover -- to accumulate and increase contractility. Perturbing this feedback results in aberrant cell junction and shape regulation, thereby compromising the ability of the tissue to buffer local mechanical fluctuations and global mechanical stresses. Altogether, we propose that differential turnover between apical and lateral polarity complexes provides an emergent mechano-response for junction length and cell shape homeostasis.

biophysics↗

bioRxiv2026

Logic of optimal collective migration in heterogeneous tissues

Collective cell migration is a critical process in embryogenesis and cancer invasion. Recent work has shown that uniform tissues can undergo sharp rheological transitions, with collective motion emerging above a critical cell motility. In vivo, however, migration typically involves multiple populations with distinct motile and adhesive properties, and how this heterogeneity shapes collective dynamics remains unclear. Here, using two different vertex model implementations, we show that migration of heterogeneous clusters through tissues is maximized at intermediate adhesion strength: too little and the cluster fragments, too much and cluster cell cohesion suppresses the rearrangements needed for forward motion. We test our model against recent and new data on zebrafish mesendoderm invasion, where graded Nodal signalling regulates both motility and adhesion differences. By mapping measured Nodal levels to mechanical parameters, the model not only reproduces migration outcomes across homogeneous and heterogeneous clusters, but also discriminates between alternative adhesion rules. Strikingly, the inferred parameters place the system near the predicted optimum, where adhesion is strong enough to maintain cohesion yet graded enough to allow selective coupling among heterogeneous neighbors. These results identify an optimal balance between cohesion and interfacial remodeling as a general principle coordinating collective invasion in heterogeneous tissues. Significance statementCells often migrate collectively during embryonic development and cancer invasion, but tissues are rarely uniform and different cells differ both in their adhesion and activity. Using models of tissue mechanics, we show that collective invasion is maximized at an intermediate level of adhesion within the migrating cluster cells: too little and the cluster falls apart, too much and it cannot advance. We test this principle against experiments in zebrafish gastrulation, where a signaling gradient simultaneously controls both cell motility and adhesion. The model reproduces migration outcomes across a range of experiments and identifies the adhesion rule cells use to selectively stick to neighbors. These results reveal a simple mechanical logic for how heterogeneous cell collectives coordinate invasion.

biophysics↗

bioRxiv2022

Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven (un)jamming

Embryo development requires both biochemical signalling generating patterns of cell fates and active mechanical forces driving tissue shape changes. Yet, how these fundamental processes are coordinated in space and time, and, especially, how tissue patterning is preserved despite the complex cellular flows occurring during morphogenesis, remains poorly understood. Here, we show that a Nodal/TGF-{beta} morphogen gradient orchestrates pattern-preserving mesendoderm internalization movements during zebrafish gastrulation by triggering a motility-driven (un)jamming transition. We find that graded Nodal signalling, in addition to its highly conserved role in mesendoderm patterning, mechanically subdivides the tissue into a small fraction of highly protrusive leader cells able to locally unjam and thus autonomously internalize, and less protrusive followers, which remain jammed and need to be pulled inwards by the leaders. Using minimal particle-based simulations and experimental perturbations, we further show that this binary mechanical switch, when combined with Nodal-dependent preferential adhesion coupling leaders to followers, is critical for triggering collective and orderly mesendoderm internalization, thus preserving tissue patterning. This provides a simple, yet quantitative, theoretical framework for how a morphogen-encoded (un)jamming transition can bidirectionally couple tissue mechanics with patterning during complex three-dimensional morphogenesis.

developmental biology↗

bioRxiv2020

Analysis of receptor-ligand pairings and distribution of myeloid subpopulations across the animal kingdom reveals neutrophil evolution was facilitated by colony-stimulating factors.

Neutrophils or heterophils constitute the largest population of phagocytic granulocytes in the blood of mammals and birds. The development and function of neutrophils and monocytes is primarily governed by the granulocyte colony-stimulating factor receptor family (CSF3R/CSF3) and macrophage colony-stimulating factor receptor family (CSF1R/IL34/CSF1) respectively. Using various techniques this study considered how the emergence of receptor:ligand pairings shaped the distribution of blood myeloid cell populations. Comparative gene analysis supported the ancestral pairings of CSF1R/IL34 and CSF3R/CSF3, and the emergence of CSF1 later in tetrapod lineages after the advent of Jawed/Jawless fish. Further analysis suggested that the emergence of CSF3 lead to reorganisation of granulocyte distribution between amphibian and early reptiles. However, the advent of endothermy likely contributed to the dominance of the neutrophil/heterophil in modern-day mammals and birds. In summary, we show that the emergence of CSF3R/CSF3 was a key factor in the subsequent evolution of the modern-day mammalian neutrophil.Impact statement Colony-stimulating factors (CSFs) are important for myeloid phagocyte development. The emergence of CSF3/CSF3R in tetrapod lineages has uniquely contributed to physical, functional and structural adaptions observed in mammalian neutrophils.Competing Interest StatementThe authors have declared no competing interest.View Full Text

immunology↗