Podocalyxin regulates pronephric glomerular development in zebrafish.
Vertebrate glomerular podocytes possess a highly sialylated transmembrane glycoprotein, Podocalyxin. In mammals, the sialic acid of Podocalyxin plays a crucial role in the formation of the characteristic podocyte architecture required for glomerular filtration. We examined the function of Podocalyxin in the developing zebrafish pronephros by disrupting the expression ofpodocalyxinthrough the use of morpholino antisense oligonucleotides. Podocalyxin was localized at the apical membrane of podocytes throughout pronephric glomerular development in zebrafish. Translational blocking ofpodocalyxinexpression resulted in pericardial edema and a hypoplastic glomerulus. Whereas regular foot processes with a slit diaphragm covered 66.7 ± 7.8% of the urinary surface of glomerular basement membrane in control fish, only 14.4 ± 7.5% of this area was covered with regular foot processes in the translationally-blocked morphants. Splice blocking ofpodocalyxinexon 2, which partially encodes the bulky mucin domain with extensive sialic acid-containing sugar chains, resulted in the deletion of 53% of mucin domain-coding sequence frompodocalyxinmRNA. Approximately 40% of these splice-blocked morphants had mild pericardial edema. Although the pronephric glomerulus in the splice-blocked morphants exhibited almost normal appearance with developed glomerular capillaries and mesangium, they had only 36.3 ± 6.9% of the area covered with regular foot processes. In conclusion, Podocalyxin is predominantly expressed in the podocytes and plays a distinct role in the formation of the podocyte foot processes with a slit diaphragm during zebrafish pronephric development.
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA ; Department of Anatomy and Life Structure, Juntendo University School of Medicine, Tokyo, Japan.
Koichiro
K
Ichimura
Rebecca
R
Powell
Tomomi
T
Nakamura
Hidetake
H
Kurihara
Tatsuo
T
Sakai
Tomoko
T
Obara
glomerulogenesis; mucin domain; podocalyxin; podocytes; pronephros; zebrafish