Biology subjects

Yung, T.

Publications and source records attributed to Yung, T..

3 recordsLinked to original sources

bioRxiv2023

Mesenchymal Wnts are required for morphogenetic movements of calvarial osteoblasts during apical expansion

Apical expansion of calvarial osteoblast progenitors from the cranial mesenchyme (CM) above the eye is integral for calvarial growth and enclosure of the brain. The cellular behaviors and signals underlying the morphogenetic process of calvarial expansion are unknown. During apical expansion, we found that mouse calvarial primordia have consistent cellular proliferation, density, and survival with complex tissue scale deformations, raising the possibility that morphogenetic movements underlie expansion. Time lapse light sheet imaging of mouse embryos revealed that calvarial progenitors intercalate in 3D to converge supraorbital arch mesenchyme mediolaterally and extend it apically. In contrast, progenitors located further apically exhibited protrusive and crawling activity. CM cells express non-canonical Wnt/Planar Cell Polarity (PCP) core components and calvarial osteoblasts are bidirectionally polarized. We found non-canonical ligand, Wnt5a-/- mutants have less dynamic cell rearrangements, protrusive activity, and a flattened head shape. Loss of cranial mesenchyme-restricted Wntless (CM-Wls), a gene required for secretion of all Wnt ligands, led to diminished apical expansion of OSX+ calvarial osteoblasts in the frontal bone primordia in a non-cell autonomous manner without perturbing proliferation or survival. Calvarial osteoblast polarization, progressive cell elongation and enrichment for actin cytoskeleton protein along the baso-apical axis were dependent on CM-Wnts. Thus, CM-Wnts regulate cellular behaviors during calvarial morphogenesis and provide tissue level cues for efficient apical expansion of calvarial osteoblasts. These findings also offer potential insights into the etiologies of calvarial dysplasias.

developmental biology↗

bioRxiv2023

Fluctuations and entropy enable neural crest cell ingression

The second law of thermodynamics explains the dissipative nature of embryonic development as an exchange of energy-dependent order for proportionately greater output of heat and waste. Recent work on granular matter provides a path by which to define the roles of passive, stochastic mechanisms in nonequilibrium systems. Here, we apply such a framework to examine the role of thermodynamic parameters to cell ingression, the movement of cells from one tissue layer to another that has been attributed, in part, to directional cues. Using the murine neural crest as a model system, we provide evidence that a stochastic mechanism, rather than a proposed stiffness gradient, underlies cell ingression. Cortical fluctuations representing effective temperature and cell packing configurations generate an entropic trap that promotes cell ingression. The results imply dissipative mechanisms that transiently disorder tissue underlie some morphogenetic events.

developmental biology↗

bioRxiv2023

Durotaxis bridges phase transition as a function of tissue stiffness in vivo

Physical processes ultimately drive morphogenetic cell movements. Two proposals are that 1) cells migrate toward stiffer tissue (durotaxis) and that 2) the extent of cell rearrangements reflects liquid-solid tissue phase. It is unclear whether and how these concepts are related. Here, we identify fibronectin-dependent tissue stiffness as a control variable that underlies and unifies these phenomena in vivo. In murine limb bud mesoderm, cells are either caged, move directionally by durotaxis or intercalate as a function of their location along a stiffness gradient. A unifying stiffness-phase transition model that is based on a Landau equation accurately predicts cell diffusivity upon loss or gain of fibronectin. Fibronectin is regulated by a WNT5A-YAP positive feedback pathway that controls cell movements, tissue shape and skeletal pattern. The results identify a key determinant of phase transition and show how durotaxis emerges in a mixed phase environment in vivo.

developmental biology↗