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Unraveling the Developing Cerebral Cortex

"We are what we think. All that we are arises with our thoughts. With our thoughts, we make the world."
- Buddha

"The empires of the future are the empires of the mind."
- Sir Winston Churchill

"Half this game is ninety percent mental."
- Yogi Berra

Whether a religious figure, statesman, or Hall of Fame catcher, nothing is more central to being "human" than the cerebral cortex. The cerebral cortex controls a dizzying array of functions, such as movement, vision, and language. Yet early in development, the cortex is little more than an undifferentiated sheet of neural stem cells (NSCs). How this simple tissue develops into what is arguably the most complex structure in the universe is one of the great questions of neuroscience. Moreover, when something goes wrong during cortical development, birth defects and common diseases such as mental retardation and epilepsy too often ensue.

The goal of our laboratory is to understand how the cerebral cortex and its NSCs develop, then apply this information to human disorders and NSC culture strategies for potential cell-based therapies. Current studies focus on the roles of morphogens and transcription factors in early NSC fate control and boundary formation involving the cortex and specialized tissues at the midline. A midline tissue of particular interest is the choroid plexus, the source of cerebrospinal fluid (CSF) and a tissue with untapped therapeutic potential. Approaches used in the lab include mouse genetics, mouse models of human disease, in utero electroporation, explants, and traditional cell cultures of mouse and human NSCs. In collaboration with other UCI labs, we are also using mathematical models to understand early forebrain development, bioengineering tools to study NSC responses to microfluidic morphogen gradients and mechanical tension, and novel strategies to sort and study NSCs based on their electrical signatures.