APP involvement in retinogenesis of mice.
Very few studies have examined expression and function of amyloid precursor protein (APP) in the retina. We showed that APP mRNA and protein are expressed according to the different waves of retinal differentiation. Depletion of App led to an absence of amacrine cells, a 50% increase in the number of horizontal cells and alteration of the synapses. The retinas of adult APP(-/-) mice showed only half as many glycinergic amacrine cells as wild-type retinas. We identified Ptf1a, which plays a role in controlling both amacrine and horizontal cell fates, as a downstream effector of APP. The observation of a similar phenotype in sorLA knockout mice, a major regulator of APP processing, suggests that regulation of APP functions via sorLA controls the determination of amacrine and horizontal cell fate. These findings provide novel insights that indicate that APP plays an important role in retinal differentiation.
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Paris 6, INSERM, 15 rue de l'Ecole de Médecine, Paris, France.
Virginie
V
Dinet
Na
N
An
Giuseppe D
GD
Ciccotosto
Julien
J
Bruban
Agathe
A
Maoui
Shayne A
SA
Bellingham
Andrew F
AF
Hill
Olav M
OM
Andersen
Anders
A
Nykjaer
Laurent
L
Jonet
Roberto
R
Cappai
Frédéric
F
Mascarelli
D000375:Aging / Q000502:physiology; D025042:Amacrine Cells / Q000166:cytology / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D051248:Retinal Horizontal Cells / Q000166:cytology / Q000502:physiology; D013569:Synapses / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D014157:Transcription Factors; C062602:transcription factor PTF1