Chenghua Gu, Ph.D.
Associate Professor of Neurobiology
- Gu Lab
Proper function of precisely wired neural circuits depends on a close physical and functional relationship with an equally complex and overlapping network of blood vessels. Blood vessels provide neurons with oxygen and nutrients and protect them from toxins and pathogens. Nerves, in turn, control blood vessel dilation and contraction and also heart rate. Key to this functional interdependence is an extraordinarily tight physical association between neurons and endothelial cells, with nearly every neuron in the human brain estimated to be supplied by its own capillary. Indeed, recent evidence suggests that neurodegenerative diseases once thought to be caused by intrinsic neuronal defects are in fact initiated and perpetuated by vascular abnormalities. However, despite the importance of this intimate relationship, how the nervous system becomes closely aligned with the vascular system during development and what molecular signals permit ongoing neurovascular interactions in the adult remains mystery. The goal of our research is to understand the molecular mechanisms of how neural and vascular networks are coordinately developed, communicated, and evolve to work in concert during normal and disease states. Investigating interactions between the vascular and nervous systems in essential for understanding nervous system function and also the underlying causes of neurological diseases.
Neurovascular biology is a relatively young field and very little is currently known. In order to elucidate the functional aspects of neurovascular interactions, such as the mechanisms underlying the coupling between neural activity and vascular dynamics or BBB formation and tightness, we must first understand and characterize the anatomical aspects of the neurovascular interactions. These basic characterizations and molecular identifications will provide important tools and premise for functional studies. Therefore my lab’s past and current research can be divided into two general directions- the mechanisms underlying the anatomical aspect of the neurovascular interactions, and the functional aspect of the neurovascular interactions. Using a combination of mouse genetics, cell biology, biochemistry, and imaging techniques, our research program currently explores 4 topics
(1) What are the molecular mechanisms underlying the establishment of neurovascular congruency?
(2) How do common guidance cues and their receptors function in wiring neural circuitry and shaping vascular topology?
(3) What are the mechanisms underlying the cross-talk between neural activity and vascular dynamics?
(4) What are the molecular mechanisms governing the formation of a functional blood brain barrier (BBB)?
To study these questions in vivo, we 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.
Neuropilin-1 functions as a VEGFR2 co-receptor to guide developmental angiogenesis independent of ligand binding. September 22, 2014. eLife.Link to Abstract
Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex. August 21, 2014. Neuron.Link to Abstract
Multiphasic modulation of cholinergic interneurons by nigrostriatal afferents. June 18, 2014. The Journal of neuroscience : the official journal of the Society for Neuroscience.Link to Abstract
An image-based RNAi screen identifies SH3BP1 as a key effector of Semaphorin 3E-PlexinD1 signaling. May 19, 2014. The Journal of cell biology.Link to Abstract
Mfsd2a is critical for the formation and function of the blood-brain barrier. May 14, 2014. Nature.Link to Abstract
Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis. April 24, 2014. eLife.Link to Abstract
Establishment of neurovascular congruency in the mouse whisker system by an independent patterning mechanism. October 16, 2013. Neuron.Link to Abstract
The role of semaphorins and their receptors in vascular development and cancer. February 17, 2013. Experimental cell research.Link to Abstract
The role and mechanism-of-action of Sema3E and Plexin-D1 in vascular and neural development. December 25, 2012. Seminars in cell & developmental biology.Link to Abstract
Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number. November 11, 2012. Nature neuroscience.Link to Abstract
Semaphorin 3E-Plexin-D1 signaling controls pathway-specific synapse formation in the striatum. December 18, 2011. Nature neuroscience.Link to Abstract
Semaphorin 3E-Plexin-D1 signaling regulates VEGF function in developmental angiogenesis via a feedback mechanism. July 1, 2011. Genes & development.Link to Abstract
VEGF mediates commissural axon chemoattraction through its receptor Flk1. June 9, 2011. Neuron.Link to Abstract
Neuropilin 1-Sema signaling regulates crossing of cingulate pioneering axons during development of the corpus callosum. April 8, 2009. Cerebral cortex (New York, N.Y. : 1991).Link to Abstract
Guidance from above: common cues direct distinct signaling outcomes in vascular and neural patterning. February 4, 2009. Trends in cell biology.Link to Abstract
Distinct roles for secreted semaphorin signaling in spinal motor axon guidance. December 22, 2005. Neuron.Link to Abstract
Guidance of trunk neural crest migration requires neuropilin 2/semaphorin 3F signaling. November 30, 2005. Development (Cambridge, England).Link to Abstract
Peripheral nerve-derived VEGF promotes arterial differentiation via neuropilin 1-mediated positive feedback. January 26, 2005. Development (Cambridge, England).Link to Abstract
Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. November 18, 2004. Science (New York, N.Y.).Link to Abstract
Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve. November 15, 2004. Genes & development.Link to Abstract
Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. July 1, 2003. Developmental cell.Link to Abstract
Characterization of neuropilin-1 structural features that confer binding to semaphorin 3A and vascular endothelial growth factor 165. March 8, 2002. The Journal of biological chemistry.Link to Abstract
Apoptotic signaling through the beta -adrenergic receptor. A new Gs effector pathway. July 7, 2000. The Journal of biological chemistry.Link to Abstract
p75 neurotrophin receptor as a modulator of survival and death decisions. May 1, 1999. Microscopy research and technique.Link to Abstract
Oligodendrocyte apoptosis mediated by caspase activation. April 15, 1999. The Journal of neuroscience : the official journal of the Society for Neuroscience.Link to Abstract
Neurotrophins in cell survival/death decisions. January 1, 1999. Advances in experimental medicine and biology.Link to Abstract
BRE: a modulator of TNF-alpha action. September 1, 1998. FASEB journal : official publication of the Federation of American Societies for Experimental Biology.Link to Abstract
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