McLean Hospital 115 Mill Street Belmont, MA 02478
Dr. Anju Vasudevan’s work on early embryogenesis of the forebrain vascular system has opened up an entirely new conceptual framework from which to view this important component of brain development. Her research focuses primarily on defining mechanisms governing central nervous system angiogenesis and how it influences key events during brain development, i.e., neurogenesis, neuronal differentiation, and migration, and shapes postnatal and adult behaviors. This work has implications for understanding and treatment of a variety of nervous system disorders like autism, epilepsy, schizophrenia, and developmental delays.
Dr. Vasudevan is the recipient of the NARSAD Young and Independent Investigator Awards and NIH awards to pursue her research. She is currently director of the Angiogenesis and Brain Development Laboratory at McLean Hospital.
Disruptions in prenatal brain development can lead to diseases or disabilities including epilepsy, autism, schizophrenia, and anxiety. Dr. Vasudevan’s Angiogenesis and Brain Development Laboratory, established in 2011, investigates the key events of brain development and the ways those can go wrong, with the long-term goal of ensuring early brain development remains on track. The lab uses a combination of developmental biology, genetics, cell biology, biochemistry, and imaging techniques in their research.
The critical prenatal processes are angiogenesis (the development of blood vessels), neurogenesis (the generation of neurons/brain cells), and neuronal migration (the movement of brain cells to the appropriate circuits).
Dr. Vasudevan’s work has shown that prenatal blood vessel development molds brain cell development—a new insight. Blood vessel-related defects that originate during the brain’s earliest developmental stages may play a role in the development of neuropsychiatric diseases in a way never before imagined. The lab is working to better understand how, why, and when this happens.
In addition, Dr. Vasudevan and her group study embryonic brain endothelial cells (the cells that line the blood vessels) in depth. These have considerable potential for intervening in the adult brain to bring about positive outcomes for repair and regeneration of new brain cells.
The anatomy of the brain’s vascular networks is as complex and fascinating as that of its neuronal networks. Yet despite the remarkable progress in the understanding of the development of neuronal networks, the mechanisms regulating central nervous system (CNS) angiogenesis are not well understood.
Based on origins, anatomical location, growth patterns, and developmental regulation, embryonic vascular networks fall into two categories—pial and periventricular—and precede neuronal networks. Interestingly, the direction of propagation of the periventricular angiogenesis gradient corresponds to the transverse neurogenetic gradient and tangential migration of GABA neurons in the embryonic telencephalon.
Recent studies in the laboratory show that periventricular endothelial cells provide critical cues to instruct neurogenesis and neuronal migration. There is remarkable endothelial cell diversity and function in the embryonic telencephalon leading to several important questions regarding specifically expressed genes in individual populations of endothelial cells based on their position in the CNS.
Furthermore, the angiogenesis, neurogenesis, and GABA neuron developmental gradients are related to one another at mechanistic levels. Intrinsic neuronal defects thus far believed to cause many neurological and psychiatric diseases like schizophrenia, epilepsy, and autism may in fact be a consequence of common molecular signals defective specifically in these endothelial cells. The goal of the research is thus to understand in detail the autonomous roles of CNS angiogenesis and its significance for brain development and disease.
Li S, Haigh K, Haigh JJ, Vasudevan A. Endothelial VEGF sculpts cortical cytoarchitecture. The Journal of Neuroscience 2013;33(37):14809-15.
Won C, Lin Z, Kumar TP, Li S, Ding L, Elkhal A, Szabó G, Vasudevan A. Autonomous vascular networks synchronize GABA neuron migration in the embryonic forebrain. Nature Communications 2013; 4:2149.
Li S, Kumar PT, Joshee S, Kirschstein T, Subburaju S, Khalili JS, Kloepper J, Du C, Elkhal A, Szabó G, Jain RK, Köhling R and Vasudevan A. Endothelial cell derived GABA signaling modulates neuronal migration and postnatal behavior. Cell Research 2017. [Epub ahead of print]
Belmont campus - Mailman Research Center, Room 312