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Developing tooth germ

Developing tooth germ

scRNA-seq

MORPHOGENESIS

A major focus of our lab is to understand how organs take their shapes. We seek to explore the genetic and signaling regulation that modulates cell behaviors and fates in order to generate correct tissue morphologies and cellular identities during development. One of our favourite subjects is the developing mouse tooth, which begins its formation as a single layered epithelium and gradually undergoes a series of morphological changes, while interacting with the underlying mesenchyme. Our lab interrogates the genetic pathway, signaling control, and cell-cell interaction that govern how this developing epithelium buckles, invaginates, turns, and forms, employing techniques, such as mouse genetics, live imaging, and single cell transcriptomics in our studies.

Adult tooth epithelium

Adult tooth epithelium

Tooth organoid

Tooth organoid

STEM CELL BIOLOGY IN THE EPITHELIUM

Once an organ is formed, it must also be maintained or repaired in order to function normally throughout the lifespan of the animal. Tissue regeneration is dependent on proper regulation of resident somatic stem cells, which first give rise to the highly-proliferative transit amplifying cells and then differentiated cells. Using the adult mouse incisor epithelium as a model, we investigate mechanisms that control the transition between these different stages and the coordination between cell proliferation and differentiation. From the signaling and genetic pathways to the cellular movement and orientation, we take a multidisciplinary approach to understand stem cell regulation in teeth and other craniofacial structures, and ultimately apply this knowledge towards organ bioengineering and regenerative medicine.

Timelapse of tooth development

Timelapse of tooth development

Force measurement in the tooth epithelium

Force measurement in the tooth epithelium

biomechanics of tooth development & regeneration

As an embryo develops and primordial organs begin to take shape, a confluence of biochemical and mechanical signals instructs constituent cells to organize into specific patterns and forms. What are the functional roles of these mechanical signals and how are forces integrated with signaling pathways to control morphogenesis? We collaborate with the research groups of Otger Campàs at Physics of Life and Ophir Klein at Cedars Sinai to use state-of-the-art biomechanical techniques to measure cellular and tissue forces during development, and combine that with mouse genetics and live imaging to investigate the mechanical regulation of organ shape acquisition.

We also study how tissue architecture and associated mechanics contribute to stem cell regulations in adult organs, focusing on understanding the roles of cell density, adhesion, and arrangement in governing epithelial cell proliferation and differentiation.

Regulation of YAP

metabolic control of craniofacial development & regeneration

We explores how cells use energy to shape the developing tooth and mandible, how metabolic activity influence mechanical forces, and how these processes work together to guide tooth formation and repair. By studying key metabolic pathways and regulation of mitochondrial functions, we aim to uncover the hidden connections between metabolism, tissue mechanics, and pattern formation. Understanding these interactions could pave the way for new strategies in tooth regeneration and the treatment of developmental disorders