Stacks Image 973

Bioimaging of Tissue Patterning and Cellular Communication during Embryonic Development

  • Stacks Image 440
    Image slide caption
  • Stacks Image 441
    Image slide caption
  • Stacks Image 442
    Image slide caption
  • Stacks Image 446
    Image slide caption
  • Stacks Image 448
    Image slide caption
  • Stacks Image 450
    Image slide caption
  • Stacks Image 515
    Image slide caption
How specific molecular signals affect individual cell behaviors to generate complex three-dimensional tissues and structures is an outstanding question. In these morphogenic processes there can be a wide variety of cell behaviors; individual cells may change shape or divide, migrate to different areas, or differentiate to form a pattern. These complex cell behaviors are orchestrated very rapidly and dynamically, often in a limited number of cells, and within the temporal constraints imposed by embryonic development. Our research seeks to decipher the underlying cell biology of tissue patterning controlling these critical cellular processes.
Stacks Image 750
With the aim to understand the mechanisms of signaling between cells and tissues, a major focus of our lab is to employ state-of-the-art high speed and high resolution imaging to uncover the earliest cell-cell interactions, signaling, and morphogenetic events in organogenesis that govern large-scale pattern formation. In particular, we have made significant advances in the development of new strategies to image living intact vertebrate embryos at single cell resolution that has not been previously possible to resolve. We also pioneered methods to stably integrate tetracycline-inducible transgenesis in chick embryos to visualize activation of entire signaling pathways at sub-cellular resolution under native regulatory control. We envision that this approach will enable us to decipher developmental control of gene expression and how signaling molecules move to provide precise spatio-temporal control of tissue development at a highly quantitative and single cell level.

How do cells communicate to build tissues?

Long-range communication among cells during embryonic development is essential for controlling the differentiation, size and shape of all organs and tissues. It has long been known that key cell signaling molecules, called morphogens, are critically required to establish such embryonic tissue patterns that eventually give rise to adult structures. However, traditional methods for visualizing how signaling molecules travel through intricate tissues to reach responding cells, predominately at lower resolution within fixed and stained tissue samples, provides only a static snapshot of a very dynamic process.

To solve this problem, we have optimized state-of-the-art live cell imaging techniques to visualize the production and reception of signaling molecules within developing vertebrate embryos. This has led to a striking and unexpected discovery in which we identified a novel means of cell-cell communication dependent on a dense network of cellular extensions, that we have termed specialized filopodia, which transverse many cell diameters and form a network of stable contacts revealing a new cellular landscape of developing vertebrate organs and tissues.
New modes of cellular communication through networks of specialized filopodia.
We have uncovered in living chick embryos a dense network of long cellular projections, or specialized filopodia, that link distant cells and traffic key signaling components (video shows mesenchymal cells within the developing limb bud).
Stacks Image 994
Specialized Filopodia Serve as Conduits for the Directed Movement and Distribution of Cargo in 3D Space. Shown is Shh visualized under native regulatory control revealing that it is produced in the form of a particle that traffics along filopodial extensions within the developing limb bud in vivo.

Meet The First Barna Lab Transgenic Chicken "Baby Junior"