RT Journal Article SR Electronic T1 Glycerophosphodiesterase GDE2 affects pancreas differentiation in zebrafish JF bioRxiv FD Cold Spring Harbor Laboratory SP 108779 DO 10.1101/108779 A1 Michiel van Veen A1 Jason van Pelt A1 Laurie A. Mans A1 Wouter H. Moolenaar A1 Anna-Pavlina G. Haramis YR 2017 UL http://biorxiv.org/content/early/2017/03/14/108779.abstract AB Notch signaling plays an essential role in the proliferation, differentiation and cell fate determination of various tissues, including the developing pancreas. One regulator of the Notch pathway is GDE2 (or GDPD5), a transmembrane ecto-phosphodiesterase that cleaves GPI-anchored proteins at the plasma membrane, including a Notch ligand regulator. Here we report that Gde2 knockdown in zebrafish embryos leads to developmental defects, particularly, impaired motility and reduced pancreas differentiation, as shown by decreased expression of insulin and other pancreatic markers. Exogenous expression of human GDE2, but not catalytically dead GDE2, similarly leads to developmental defects. These data reveal functional conservation between zebrafish and human GDE2, and suggest that strict regulation of GDE2 expression and catalytic activity is critical for correct embryonic patterning. In particular, our data uncover a role for GDE2 in regulating pancreas differentiation.