Our group is interested in studying how the behaviors of individual cells contribute to the formation of tissue patterns. This is an essential process required for the development, homeostasis, and regeneration of living tissues. We use the fruit fly, Drosophila Melanogaster, as a model organism alongside genetics, microscopy, and quantitative analyses to ask questions like:
How do cells communicate with each other during patterning events?
How does cell shape and movement affect cell-cell communication?
Are there rules that individual cells follow to make fate decisions during patterning?
How do these processes contribute to the self-organization of the tissue?
We currently have students investigating the role of Myosins in the cell shape changes that are essential for Notch-mediated lateral inhibition. We also are investigating the role of Notch interactors on pattern formation. We have plans to pursue collaborative experiments using mathematical modeling and tissue engineering strategies to investigate what factors help drive different patterns and how we can manipulate these factors to change the dynamics and output of patterning processes.
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Talking to your neighbors across scales: Long-distance Notch signaling during patterning
In this review, we summarize the theoretical and experimental evidence for mechanisms that modify the scale of Notch-mediated lateral inhibition. We focus on how cell protrusions, in addition to other cell behaviors like proliferation and neighbor exchange, allow for Notch signaling to both extend lateral inhibition beyond nearest neighbors and impact the timescale of patterning.
Phosphorylation and Proteolytic Cleavage of Notch in Canonical and Noncanonical Notch Signaling
The Notch signaling pathway is deceptively simple, but can contribute to a diverse array of biological functions. In this review, we broke down two key events in Notch signaling: proteolytic cleavage and phosphorylation.
Hunter and Giniger, 2020 Notch Signaling in Embryology and Cancer
A role for actomyosin contractility in Notch signaling
The mechanism of Notch activation requires a force producing step. We wondered whether the activity of non-muscle myosin II on the actin cytoskeleton, which can produce forces in cells, played a role in this process. Using the developing fly bristle pattern and tools in cell culture, we find that myosin II activity is important for normal Notch signaling and pattern formation.
Hunter et al, 2019 BMC Biology
Coordinated control of Notch-Delta signalling and cell division aids lateral inhibition mediated tissue patterning
What 'locks in' a pattern as it develops? Here we found that cells communicating to each other during bristle patterning are only allowed to signal to each other until they divide into two daughter cells. The Notch signaling that occurs is linked to the progression of the cell cycle. We used genetics and mathematical models to show that if you unlink these two processes, the pattern is disrupted.
Hunter et al, 2016 Development
Ion channels contribute to the regulation of cell sheet forces during Drosophila dorsal closure
How do noisy, individual cell behaviors coordinate to drive a smooth, robust, tissue movement? We identified several genes encoding channel subunits associated with mechanically gated ion channels that regulate cell shape and tissue tension generation during a morphogenetic process in fruit fly embryogenesis.
Hunter et al, 2014 Development