The GUOFA LIU LAB at the Department of Molecular, Cellular and Developmental Biology, University of Toledo is dedicated to conducting groundbreaking research in developmental neuroscience. Our team is focused on unraveling the complexities of the developing nervous system to advance our understanding of neurodevelopmental disorders.
RESEARCH
Intracellular signal transduction cascades mediating neuronal guidance. Coordination of different guidance cues, their receptors, and intracellular signal transduction cascades is crucial for neurons to find their targets and establish distinct neuronal circuits. Netrin-1 is a prototypical guidance cue for projecting axons and migrating neurons. We are currently untangling: 1) the collaboration of different Netrin receptors in axon elongation, branching, and guidance; 2) the coordination of downstream signaling cascades of Netrin receptors; 3) the coordination of Netrins with other guidance cues, such as Semaphorins, Slits, and ephrins, in the developing nervous system.
Immunocytochemistry of dissociated neuron
Cytoskeletal modulation in neuronal guidance. Modulation of actin and microtubule (MT) dynamics in the growth cone of developing neurons plays a crucial role in axon guidance and neuronal migration. However, whether MT dynamics is directly or directly involved in these processes is unclear. Our recent studies have suggested a novel working model that guidance receptors directly couple MT dynamics in neuronal guidance. We are currently investigating how guidance cues modulate MT dynamics through coupling of their receptors with dynamic MT subunits and microtubule-associated proteins in attractive and repulsive signaling.
A transverse section showing double-electroporation of Venus:Math1 and RFP in the developing chicken spinal cord
Involvement of small RNAs in axon guidance. We are interested in exploring the role of small RNAs, particularly microRNAs, in regulating guidance receptor expression during axon guidance. In spinal commissural axon projection, receptors for both attractive and repulsive guidance cues are essential for directing axonal growth cone navigation. Using chicken and mouse models, we aim to investigate the role of microRNAs in regulating these receptors, providing insights into the molecular mechanisms governing axon guidance and neural development. This research could offer a deeper understanding of neural patterning and open up potential therapeutic avenues for neurological disorders.
Axon guidance and neurological disorders. Axon guidance, a critical process during neural development where neurons extend axons to reach their target cells. Proper axon guidance is essential for the formation of functional neural circuits. Disruptions in this process can lead to a variety of neurological disorders, including lissencephaly, congenital mirror movements, cerebral palsy, horizontal gaze palsy with progressive scoliosis, congenital hydrocephalus (X-linked), autism, intellectual disabilities, spinal cord injury recovery deficits, and neurodegenerative diseases. By studying the molecular mechanisms underlying axon guidance, we aim to uncover crucial insights that could inform the development of innovative therapeutic strategies for these conditions.
A transverse section showing over-expression of microRNA with Venus:Math1 in the developing chicken spinal cord
A transverse section of mouse spinal cord after immunohistochemistry (E11.5)
Developing chicken embryo after whole mount in situ hybridization (HH 23-25)
Explant co-culture of a turning assay
