Our Mission

Morphogenesis is controlled primarily by local coordinated changes of cell shape, rearrangements of cell-cell contacts, cell proliferation and cell death. The genes and molecular mechanisms that regulate these cellular behaviors are only partially characterized. Therefore, a major goal is to identify novel genes that participate in tissue morphogenesis and elucidate their mechanism of function. Anomalies in epithelial morphogenesis underlie a range of congenital diseases such as spina bifida, cystic kidneys and vascular aneurysm, and acquired diseases such as cancer that disrupt the normal morphology of tissues and organs. To understand these disease processes a deep understanding of the mechanisms involved is essential.

Coordinated cell behaviors drive tissue morphogenesis

Mechanical forces generated by cell proliferation, apoptosis, cell-cell adhesion and the cytoskeleton drive morphogenesis. However, the modulation of mechanical force generation in space and time by extracellular signals, polarized membrane landmarks and cytoskeletal effectors are just being elucidated. The convergence of recent advances in imaging technologies, fluorescent reporters, computational image analysis and mathematical modeling enables developmental biologists to observe and define the molecular and cellular basis of morphogenetic processes with unprecedented detail.

Our lab investigates the morphogenesis of the epithelium of imaginal discs of fruit fly Drosophila as a model system. The imaginal discs are set aside from the embryonic epidermis during embryonic development. During larval stages, secreted signals called morphogens that emanate from localized signaling centers promote proliferation of epithelial cells and specify the cellular identities of the various parts of adult appendages. During post-larval stages the imaginal discs undergo extensive remodeling to generate the final shape of adult appendages.

Morphogenesis of the leg imaginal disc is a model for epithelial elongation by cell shape changes and rearrangements of cell-cell contacts.

The fly eye is composed of ~800 ommatidial units. Shown is a single ommatidium at 28 and 40h after puparium formation (APF). Each ommatidial unit is composed of a core of eight photoreceptors (not shown in the image) capped by four cone cells and surrounded by two large semi-circular 1° cells. A single file of lattice cells (LCs) surrounds each ommatidial unit. At early stages the LCs are isometric but as development proceeds the 2° LCs narrow and elongate to form the edges of the lattice, the 3° LCs compact to form every other corner of the lattice, while sensory bristles cells occupy adjacent corners. During this process superfluous LCs die and delaminate from the epithelium. Our lab employs the eye imaginal disc to investigate how mechanical forces generated by cell adhesion and by contractile and protrusive cytoskeletal proteins regulate cell shape changes and cell death, and how extracelluar signals and polarity proteins regulate mechanical force generation in space and time.

Epithelial morphogenesis involves cell slippage, cell shape changes, cell division and cell death in tissues that consist of hundreds to thousands of cells. The quantitative analyses of these behaviors at a system level require computational tools to identify cells and follow their behavior. Our lab develops computational tools to follow cell behavior in time-lapse movies and identify lineage relationships among cells. We recently developed ttt is a tissue tracker, a computational pipeline designed to (A-B) segment apical outlines of epithelial cells in 3D, (C-D) track the motion of cell centroids, and detect (E) mitosis and (F) apoptosis.

Check ttt project page for more information

Analysis of tissue mechanics using non-invasive approaches