401B, Life Sciences Center
“Shaping” of the developing organism and its component tissues and organs, better known as morphogenesis, is vital to formation of the embryo. When normal morphogenetic processes go awry, birth defects are the probable outcome. Understanding the molecular mechanisms that underlie formation of body plan, tissues and organs during normal development further serves as a map for prospective tissue engineering applications. Additionally, cellular movements that occur during development may be recapitulated later in life as a contributing factor to pathological conditions, such as cancer, or as part of the body’s response to trauma, as in wound healing.
Key Areas of Research Interest:
- Understanding how cells perceive and respond to physical cues in their environment
- Force-dependent changes in cytoskeleton organization and related cell signaling
- How do individual cell behaviors alter the intrinsic micromechanical properties of tissues to alter morphogenetic movements?
The Weber Laboratory uses the African clawed frog, Xenopus laevis, as a model organism for studying developmental biology, molecular signaling pathways and cellular behaviors. Several advantages are offered by the Xenopus system:
- Ability to manipulate gene expression via microinjection of RNA transcripts and/or antisense morpholino oligonucleotides
- Ease of culturing without serum or other added factors
- Ability to make explants of whole tissues that retain normal developmental programming, including morphological movements and gene expression patterns
Using tissues from the developing Xenopus embryo, we study how adhesive interactions between cells influence their behavior. Cells interact with each other, in part, through adhesion molecules expressed on the cell surface. In the early Xenopus embryo, the calcium-dependent receptor C-cadherin enables cells to cohesively adhere to one another, providing a transmembrane connection between the extracellular environment and the intracellular cytoskeleton. In addition to serving as a primary physical basis for the cohesion of cells, cadherins also modulate cell signaling by serving as a platform for macromolecular complexes, including kinases, phosphatases, scaffolding proteins and the cytoskeleton. The Weber Laboratory is interested in the problem of how cells are able to detect forces on adhesive contacts and react to these stimuli to effect cell polarity and migration.
Morphogenetic events of early development are driven by the movement of whole tissues. Whole tissue migration involves the coordinated movement of large populations of cells, so-called collective cell migration. These cohesive cells push and pull against one another, creating dynamic physical cell-on-cell interactions that have unique consequences on cell and tissue behavior. Our prior research demonstrated that mechanical pulling on cadherin adhesions signals directional cell protrusive behavior (Weber, Bjerke and DeSimone, 2012). Furthermore we identified keratin intermediate filaments as a necessary component of the cadherin mechanosensory complex.
We are now investigating how keratin intermediate filaments contribute to this signaling mechanism. Current strategies are focused on identifying the signaling and physical links between the cadherin-keratin mechanosensory complex and the actin cytoskeleton that mediates cell protrusions. Using state-of-the-art techniques, including live-cell high-resolution confocal microscopy, protein strain biosensors, and magnetic bead pull assays, we examine real-time cytoskeletal reorganization and molecular signaling processes involved in mechanical induction of collective cell migration. The goal is to determine how cells biochemically and biophysically interact with neighboring cells to coordinate cell migration and produce gross tissue movements, essential to both development and disease.
B.S. in Biology, Ursinus College, 2000
Ph.D. in Molecular Cell Biology, Thomas Jefferson University, 2006
Batra N, Burra S, Siller-Jackson AJ, Gu S, Xia X, Weber GF, DeSimone D, Bonewald LF, Lafer EM, Sprague E, Schwartz MA, Jiang JX. “Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels.” Proceedings of the National Academy of Sciences. 109(9):3359-64, 2012 Feb 28.
Weber GF, Bjerke MA, DeSimone DW. "A mechanicoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration." Developmental Cell. 22(1):104-115, 2012 Jan 17.
Weber GF, Bjerke MA, DeSimone DW. “Integrins and cadherins join forces to form adhesive networks.” Journal of Cell Science. 124(Pt 8):1183-93, 2011 Apr 15.
Rozario T, Dzamba B, Weber GF, Davidson LA, DeSimone DW. “The physical state of fibronectin matrix differentially regulates morphogenetic movements in vivo.” Developmental Biology. 327(2):386-98, 2009 Mar 15.
Weber GF, Menko AS. “Phosphatidylinositol 3-kinase is necessary for lens fiber cell differentiation and survival.” Investigative Ophthalmology and Visual Science. 47(10):4490-9, 2006 Oct.
Weber GF, Menko AS. “Actin filament organization regulates the induction of lens cell differentiation and survival.” Developmental Biology. 295(2):714-29, 2006 Jul 15.
Weber GF, Menko AS. “The canonical intrinsic mitochondrial death pathway has a non‑apoptotic role in signaling lens cell differentiation.” Journal of Biological Chemistry. 280(23):22135-45, 2005 Jun 10.
Weber GF, Menko AS. “Color image acquisition using a monochrome camera and standard fluorescence filter cubes.” BioTechniques. 38(1):52-3, 2005 Jan.