Biology subjects

Lattner, J.

Publications and source records attributed to Lattner, J..

4 recordsLinked to original sources

bioRxiv2025

Oxygen availability and hypoxia-independent action of HIF1α controls human trophoblast maturation and function

Placenta progenitor cells, also known as trophoblasts, initially specify at very low oxygen (O2) concentrations. Across their differentiation path in the uterine microenvironment, they encounter a wide range of O2 levels. Despite previous efforts, dissecting how these rapid and dynamic O2 levels are sensed by trophoblast stem cells and transduced via hypoxia inducible factors (HIFs) has been challenging and has led to conflicting conclusions. This is at least in part due to the lack of tractable and reliable methods to model human placental development. Here, by recapitulating the dynamic O2 levels of the uterine microenvironment, and by genetically ablating HIF1 in human trophoblast organoids, we found that O2 availability and HIF pathway independently control trophoblast lineage specification, maturation and function. Specifically, low O2 levels promote expansion of extravillous trophoblast (EVT) progenitors independently of HIF1, while HIF1 is necessary for EVT invasion regardless of O2 availability. Altogether, our results reveal a dual regulatory framework that disentangles the role of O2 from that of HIF1, offering a revised view of how O2 availability regulates early human placental development.

developmental biology↗

bioRxiv2023

Multifractal signatures in ossification reveal a disordered-to-ordered transition in mineral pattern

Developing biological systems can exhibit both dynamic pattern formation and cross-scale interactions. Multiscale relationships are critical in the establishment of these patterns but remain poorly understood. Classification of mineral pattern in bone is a quintessential example. One approach to quantifying these patterns relies upon statistical self-similarity and, in particular, monofractal analysis. However, simple monofractal characterisations fail to capture the complexity of multiscale interactions in developing biological systems. Here we show that multifractal techniques, effectively capture the complex patterns of self-similarity in a dimensionally reduced, usable way. Further, we show that a simple generative model of ossification in the mouse skull, coupled with multifractal methods indicates a primary role of collagen density in pattern establishment and predicts the existence of a sharp boundary in pattern complexity.

biophysics↗

bioRxiv2023

Self-propagating wave drives noncanonical antidurotaxis of skull bones in vivo

Cell motility is a key feature of tissue morphogenesis, and it is thought to be driven primarily by the active migration of individual cells or collectives. However, this model is unlikely to apply to cells lacking overt cytoskeletal, stable cell-cell or cell-cell adhesions, and molecular polarity, such as mesenchymal cells. Here, by combining a novel imaging pipeline with biophysical modeling, we discover that during skull morphogenesis, a self-generated collagen gradient expands a population of osteoblasts towards a softer matrix. Biomechanical measurements revealed a gradient of stiffness and collagen along which cells move and divide. The moving cells generate an osteogenic front that travels faster than individual tracked cells, indicating that expansion is also driven by cell differentiation. Through biophysical modeling and perturbation experiments, we found that mechanical feedback between stiffness and cell fate drives bone expansion and controls bone size. Our work provides a mechanism for coordinated motion that does not rely upon the cytoskeletal dynamics of cell migration. We term this self-propagating motion down a stiffness gradient, noncanonical antidurotaxis. Identification of alternative mechanisms of cellular motion will help in understanding how directed cellular motility arises in complex environments with inhomogeneous material properties.

biophysics↗

bioRxiv2019

Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P2 in Drosophila

An efficient vectorial intracellular transport machinery depends on a well-established apico-basal polarity and is a prerequisite for the function of secretory epithelia. Despite extensive knowledge on individual trafficking pathways, little is known about the mechanisms coordinating their temporal and spatial regulation. Here, we report that the polarity protein Crumbs is essential for apical plasma membrane phospholipid-homeostasis and efficient apical secretion. Through recruiting {beta}Heavy-Spectrin and MyosinV to the apical membrane, Crumbs maintains the Rab6-, Rab11- and Rab30-dependent trafficking and regulates the lipid phosphatases Pten and Ocrl. Crumbs knock-down results in increased apical levels of PI(4,5)P2 and formation of a novel, Moesin- and PI(4,5)P2-enriched apical membrane sac containing microvilli-like structures. Our results identify Crumbs as an essential hub required to maintain the organization of the apical membrane and the physiological activity of the larval salivary gland.

cell biology↗