Bryce LaFoya

Stem cells, brain development and regeneration, membrane and cytoskeleton dynamics, Danionella fish and Drosophila, super-resolution microscopy

Brain Development and Regeneration

Neural stem cells are the architects of the brain, shaping its development and repair in complex ways that continue to surprise us. We examine their inner workings by bridging the disciplines of cell biology, development, and neurobiology to uncover how these remarkable cells orchestrate the construction of brain tissue. Using animal models like the fruit fly (Drosophila) and the highly transparent fish (Danionella), we leverage advanced imaging techniques to observe brain development in vivo. We also investigate how fish can regenerate their brains after injury, with the goal of unlocking secrets that could revolutionize regenerative medicine.

Our Approach: Precision Imaging, Profound Insights

Through super-resolution spinning disk microscopy, we film the vibrant, fast-paced world of neural stem cells in action. This imaging enables us to visualize the activity of proteins and subcellular structures that drive the rapid, coordinated processes underlying brain formation and regeneration.

Using these powerful tools and models, our research is currently focused on three key areas:

• Sculpting Stem Cells: Membrane and Cytoskeletal Dynamics

  Cellular function and behavior are intrinsically linked to cell morphology, the shape and form of a cell. Neural stem cells dramatically transform their morphology through the various steps of brain construction, demonstrating a tight relationship between form and function. This morphological plasticity, driven by cytoskeletal forces, remodels the plasma membrane to support specific developmental tasks, such as cell division and cellular communication. We are working to unravel the molecular mechanisms that drive these continuous morphological changes in neural stem cells as they build brain tissue.

• The Stem Cell Midbody: Directing Brain Development at the Crossroads of Cytokinesis and Fate Specification

  Building a brain cell by cell demands a delicate balance: maintaining the supply of “master builder” neural stem cells while also creating the neurons that are the brain’s functional units. Central to achieving this balance is asymmetric cell division, a specialized process by which neural stem cells generate two distinct sibling cells with different fates. During this type of division, fate specification mechanisms assign a distinct future identity to each sibling: one is set on the path to becoming a neuron, while the other retains its stemness. We have identified a novel mediator of the fate specification process that is built right into the division process: the midbody. The midbody is a structure that forms during the late stages of cytokinesis between the separating sibling cells. Our research shows that the midbody’s structural and signaling properties are crucial for proper fate specification in neural stem cell divisions. Moving forward, we aim to shed light on how disruptions in midbody function may contribute to developmental brain disorders.

• The Transparent Truth About Brain Regeneration: Danionella’s Gift to Neuroscience

  Humans, like other mammals, exhibit limited tissue regeneration, particularly in the brain. This lack of regenerative ability makes traumatic injury and neurodegenerative disease especially devastating. However, within the animal kingdom there are examples of highly regenerative animals capable of efficient brain repair through neural stem cell activity, providing hope that studying the neural stem cells of these animals can reveal how to activate brain regeneration in humans. While the mechanisms of stem cell-driven brain repair are generally hidden beneath layers of tissue and bony skulls in most regenerative vertebrates, Danionella fish stand out as a fortunate exception. Their remarkable transparency and unique inherent anatomical features, including the absence of a skull roof, offer a clear window into the adult brain. This allows for non-invasive confocal imaging of living brains, providing real-time observations into how stem cells coordinate repair processes after injury and disease. Leveraging the direct window to observing brain regeneration in Danionella, we aim to generate insights that will inform therapeutic strategies for repairing human brains ravaged by injury, neurodegenerative disorders, and aging.