Loss of the cholesterol-binding protein prominin-1/CD133 causes disk dysmorphogenesis and photoreceptor degeneration.
Prominin-1/CD133 (Prom-1) is a commonly used marker of neuronal, vascular, hematopoietic and other stem cells, yet little is known about its biological role and importance in vivo. Here, we show that loss of Prom-1 results in progressive degeneration of mature photoreceptors with complete loss of vision. Despite the expression of Prom-1 on endothelial progenitors, photoreceptor degeneration was not attributable to retinal vessel defects, but caused by intrinsic photoreceptor defects in disk formation, outer segment morphogenesis, and associated with visual pigment sorting and phototransduction abnormalities. These findings shed novel insight on how Prom-1 regulates neural retinal development and phototransduction in vertebrates.
Zacchigna
Serena
S
Vesalius Research Center, Vlaams Instituut voor Biotechnologie, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Oh
Hideyasu
H
Wilsch-Bräuninger
Michaela
M
Missol-Kolka
Ewa
E
Jászai
József
J
Jansen
Sandra
S
Tanimoto
Naoyuki
N
Tonagel
Felix
F
Seeliger
Mathias
M
Huttner
Wieland B
WB
Corbeil
Denis
D
Dewerchin
Mieke
M
Vinckier
Stefan
S
Moons
Lieve
L
Carmeliet
Peter
P
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010455:Peptides / Q000235:genetics*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000002:abnormalities* / Q000378:metabolism* / Q000503:physiopathology; D012161:Retinal Artery / Q000002:abnormalities / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D012168:Retinal Pigments / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014785:Vision, Ocular / Q000235:genetics
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; C000606024:Prom1 protein, mouse; D012168:Retinal Pigments; D002784:Cholesterol