PiN Faculty Member - Maria Lehtinen, PhD

Maria Lehtinen, PhD

Associate Professor in Pathology

Boston Children's Hospital
Enders Bldg. Room 1150
320 Longwood Avenue
Boston, MA 02115
Tel: 617-919-3504
Fax: 617-730-0168
Email: maria.lehtinen@childrens.harvard.edu
Visit my lab page here.



Our ultimate goal is to understand how the cerebrospinal fluid provides an adaptive and instructive signaling niche for the developing, adult, and aging brain. The neural precursor cells that build the developing brain are remarkably synchronized, yet no central command coordinating this process has been identified. Neural precursors divide immediately adjacent to cerebrospinal fluid (CSF)-filled ventricles and extend primary cilia into the CSF, suggesting that the cerebrospinal fluid may play an important role in instructing brain development. Our research recently revealed that the CSF proteome is both elaborate and dynamic, and that in addition to its passive role as a fluid cushion for the brain, the CSF actively provides a rich and adaptive library of secreted factors that help coordinate neurogenesis.

We found that during embryonic brain development, secreted factors in the CSF bind to receptors located along the apical, ventricular surface of progenitor cells, thus providing instructive cues that activate signaling pathways in these cells. Many signals in the CSF demonstrate age-dependence. For example, the expression of Igf2 in CSF peaks during embryonic brain development, during which it binds to its receptors located on the surface of neural precursor cells and instructs neural precursors to divide. Much of the proliferative effect of CSF is attributable to Igf2, but the CSF is a rich source other signaling activities as well. The ability of choroid plexus-secreted factors in the CSF to stimulate signaling in precursors relies on appropriately positioned signaling machinery at the ventricular surface. Our findings raise many exciting questions about the basic biology of the choroid plexus brain barrier and the brain-CSF interface during development. We are also committed to investigaitng how missteps in the regulation of the choroid plexus-CSF system contributes to neurodevelopmental conditions including hydrocephalus, neurodevelopmental diseases (e.g. autism, schizophrenia), and brain cancer. We employ diverse experimental approaches that draw on molecular and developmental neuroscience, biochemistry, genetics, and imaging.



Last Update: 12/5/2018



Publications

For a complete listing of publications click here.

 


 



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