Neurobiology

Chenghua Gu, D.V.M., Ph.D.

Assistant Professor of Neurobiology

Nervous and vascular systems share many features, despite their distinct functions. Developmentally, they are formed around the same time, and both continue to dynamically remodel throughout life. Anatomically, they are both highly- branched and complicated networks; yet both networks have remarkably stereotyped patterns. Moreover, even from the time of Vesalius and Da Vinci, it has been clear that nerves and vessels often run adjacent to each other. Functionally, neural activity and vascular dynamics are interdependent in the periphery and tightly coupled in the brain. Despite the importance of this intimate relationship, little is known at the molecular level about how these two systems are coordinately patterned during development and what permits ongoing neurovascular interactions in the adult. The goal of our research is to understand the molecular mechanisms of how neural and vascular networks are coordinately developed, communicate, and evolve to work in concert during normal and disease states.

Using a combination of mouse genetics, cell biology, and biochemistry-based approaches, our research program currently explores 4 topics:

1. Characterize the intriguing neurovascular anatomical relationship in the brain.
2. Identify the molecular signaling cascade controlling neural and vascular patterning and their intercommunication.
3. Identify novel factors from endothelial cells that control neuronal function and vice versa.
4. Address how patterning cues influence human disease, involving both neural and vascular damage and repair.

To study these questions in vivo, we frequently use genetically engineered mouse models with specific mutations and tracers combined with imaging and physiological approaches. To complement this work, we also perform studies in chick and a variety of in vitro assays to further reveal the mechanisms of action. With these approaches, we aim to understand the neurovascular interactions from a molecular level to a systems level.

An example of neurovascular congruency.  An E11.5 mouse embryo was immunostained with anti-neurofilament (red) for spinal nerves and anti-PECAM (green) for intersomitic vessels.   Our work revealed the molecular determinants and mechanisms that control the neurovascular congruency.  In this case, intersomitic vessel and spinal nerve congruency does not result from vessels following nerves or nerves following vessels.  Instead, it is achieved through a co-patterning mechanism by environmental cues secreted from the somite.  Sema3E from the somite interacts with its receptor plexin-D1 in the endothelial cells to control intersomitic vessel patterning, while Sema3A and 3F in the somite interacts with neuropilin-1/2 to control spinal nerve projections.  The coordinate interaction of both sets of ligands and receptors ensures congruency is established during development.