Key Publications

My work addresses a fundamental question in developmental biology: how is the body axis established in the mammalian embryo? I discovered a novel mechanism initiated by an early asymmetry in the basement membrane, a specialized extracellular matrix (ECM). My findings show that localized expression of a matrix metalloproteinase creates mechanical anisotropy in this structure. This spatially-defined change in matrix properties provides a guidance cue for the collective migration of the distal visceral endoderm (DVE), the symmetry-breaking event that defines the anterior end of the embryo. My work establishes a conserved principle, in mouse and human embryogenesis, whereby the physical microenvironment orchestrates mammalian body axis determination.

The shape of an organ is critical to its function, yet how this architecture arises remains a central question. My colleagues and my research challenges existing models by demonstrating that extrinsic mechanical cues from the extracellular matrix (ECM) are a dominant force in this process. I have shown that tissue morphogenesis is directly guided by ECM stiffness, which is interpreted by cells through a mechanosensitive Src tyrosine kinase pathway. This signaling cascade culminates in the reorientation of a select population of cells, collectively driving tissue elongation. My findings establish a clear mechanistic link between the physical properties of the microenvironment and the precise collective cell behaviors that sculpt developing organs.

Cell migration is indispensable to morphogenetic movements for animal development, wound healing process for homeostasis, and metastasis during pathological progression. However, tracing movements of an individual cell or collectively migrating cells in non-transparent systems in vivo remains a challenge. I developed a novel tool in Drosophila that reveals past cell migratory trajectories in fixed samples. The concept is generally applicable to reveal long-term migration trajectories during tissue and organ development of various model systems and cancer cells in metastasis and colonization.