Mentor: Dr. Edwin Monuki
The telencephalic choroid plexus epithelium (tCPe), which is located in the dorsal midline (DM) of the forebrain, is a simple epithelium that secretes cerebrospinal fluid that bathes the brain and spinal cord and functions in brain development, physiology, and neurological diseases. Despite this significance, relatively little is known about the mechanisms underlying its development. Our previous studies suggest that Bmp4 is necessary and sufficient to induce tCPe formation in the DM. Fgf8, which is expressed in the rostral midline, is known to impart positional information in the developing forebrain, and it has been shown to interact antagonistically with Bmps. Therefore my hypothesis is that Fgf signaling inhibits the tCPe cell fate by inhibiting Bmp signaling. To test this hypothesis, I used dissociated mouse neural precursor cell (NPC) cultures treated with Bmps and/or Fgf2 or Fgf8 to identify signaling interactions between Bmps and Fgfs. Semi-quantitative real-time PCR was used to quantify expression levels of tCPe and DM genes normally induced by Bmp signaling. I found that Fgf2 specifically suppresses Bmp induction of midline genes in NPC cultures taken from embryonic day 12.5 (E12.5) embryos. In E10.5 and E12.5 NPC cultures, I found that Fgf8 activates DM genes. These results demonstrate that specific signaling interactions between Bmps and Fgfs can regulate the expression of tCPe and DM genes in culture, and that Fgf2 and Fgf8 may serve different functions at different time points during DM development.