Migratory Behavior of Cortical Precursor Cells in BMP4 Microfluidic

Characterization of Cortical Precursor Cells’ Responses to BMP4 Gradient in a
Microfluidic Device
Student: Eric Kuo
Mentor: Edwin S. Monuki & Noo Li Jeon
Morphogen gradients are fundamental to animal development, and morphogen defects
are primary causes of human brain malformations. Nonetheless, tremendous controversy
remains about the mechanisms by which morphogen gradients act on the developing
brain. To date, studies on this issue have relied on traditional cell culture tools, which are
inefficient and biologically limited as models of natural gradients. In this study, a
microfluidic culture device has been engineered and optimized to address these
limitations. The device is used to simulate an in vivo environment by generating several
diverse, stable, and continuous gradient profiles onto cultured cells in which its behaviors
can be captured by time-lapse microscopy. The specific morphogen protein used in this
study is BMP4 (Bone Morphogen Protein). Our finding indicates cells exposed to high
BMP4 concentration induces cell death and suppresses cell proliferation. Also, it appears
that BMP4 us a chemo-attractant for the mNSC (mouse Neural Stem Cells), which has
never been reported in the literature. We have generated a real-time optical assay on cell
death and on proliferation in a morphogen gradient that has revealed novel insights on the
slope of the gradient and new roles of BMP4 in the developing cerebral cortex.