Core fucosylation is required for midline patterning during zebrafish development.
Complex carbohydrates represent one of the most polymorphic classes of macromolecules, but their functions during embryonic development remain poorly defined. Herein, we show that knockdown of FucT8, the fucosyltransferase responsible for adding an α1,6 fucosyl residue to the core region of N-linked oligosaccharides, results in defective midline patterning during zebrafish development. Reduced FucT8 expression leads to mild cyclopia, small forebrains, U-shaped somites, among other midline patterning defects. One of the principal FucT8 substrates was identified as Apolipoprotein B (ApoB), the major scaffold protein that is responsible for assembly and secretion of lipoprotein particles in vertebrates. In Drosophila, lipoprotein particles are thought to facilitate cell signaling by serving as a transport vehicle for lipid-modified cell signaling proteins, such as hedgehog. In this regard, knockdown of ApoB expression in zebrafish embryos leads to similar midline patterning defects as those seen in FucT8 morphant embryos. Furthermore, preliminary studies suggest that ApoB facilitates Sonic hedgehog signaling during zebrafish development, analogous to the function of lipoprotein particles during hedgehog signaling in Drosophila.
Department of Cell Biology, Emory University, Atlanta, Georgia, USA.
Anandita
A
Seth
Quentin J
QJ
Machingo
Andreas
A
Fritz
Barry D
BD
Shur
D000818:Animals; D030801:Animals, Genetically Modified; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D001055:Apolipoproteins B; D053823:Hedgehog Proteins; D029961:Zebrafish Proteins; D005647:Fucosyltransferases