Skip to main content
Top
Published in: Acta Neuropathologica 3/2011

01-03-2011 | Original Paper

APP involvement in retinogenesis of mice

Authors: Virginie Dinet, Na An, Giuseppe D. Ciccotosto, Julien Bruban, Agathe Maoui, Shayne A. Bellingham, Andrew F. Hill, Olav M. Andersen, Anders Nykjaer, Laurent Jonet, Roberto Cappai, Frédéric Mascarelli

Published in: Acta Neuropathologica | Issue 3/2011

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Andersen OM, Reiche J, Schmidt V et al (2005) Neuronal sorting protein-related receptor SorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci USA 102:13461–13466CrossRefPubMed Andersen OM, Reiche J, Schmidt V et al (2005) Neuronal sorting protein-related receptor SorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci USA 102:13461–13466CrossRefPubMed
2.
go back to reference Baba K, Sakakibara S, Setsu T, Terashilma T (2007) The superficial layers of the superior colliculus are cytoarchitectually and myeloarchitectually disorganized in the reelin-deficient mouse, reeler. Brain Res 1140:205–215CrossRefPubMed Baba K, Sakakibara S, Setsu T, Terashilma T (2007) The superficial layers of the superior colliculus are cytoarchitectually and myeloarchitectually disorganized in the reelin-deficient mouse, reeler. Brain Res 1140:205–215CrossRefPubMed
3.
go back to reference Cappai R, Barnham Kj (2008) Delineating the mechanism of Alzheimer’s disease A beta peptide neurotoxicity. Neurochem Res 33:526–532CrossRefPubMed Cappai R, Barnham Kj (2008) Delineating the mechanism of Alzheimer’s disease A beta peptide neurotoxicity. Neurochem Res 33:526–532CrossRefPubMed
4.
go back to reference Cepko CL, Austin CP, YANG X, Alexiades M, Ezzeddine D (1996) Cell fate determination in the vertebrate retina. Proc Natl Acad Sci USA 93:589–595CrossRefPubMed Cepko CL, Austin CP, YANG X, Alexiades M, Ezzeddine D (1996) Cell fate determination in the vertebrate retina. Proc Natl Acad Sci USA 93:589–595CrossRefPubMed
5.
go back to reference Cepko CL (1999) The role of intrinsic and extrinsic cues and bHLH genes in the determination of retina cell fates. Curr Opin Neurobiol 9:37–46CrossRefPubMed Cepko CL (1999) The role of intrinsic and extrinsic cues and bHLH genes in the determination of retina cell fates. Curr Opin Neurobiol 9:37–46CrossRefPubMed
6.
go back to reference Chen ST, Wang JP, Chien CH, Shen CL (1999) Differential expression of beta-amyloid precursor and Bcl-2 proto-oncogene proteins in the developing dog retina. Neurosci Res 35:265–271CrossRefPubMed Chen ST, Wang JP, Chien CH, Shen CL (1999) Differential expression of beta-amyloid precursor and Bcl-2 proto-oncogene proteins in the developing dog retina. Neurosci Res 35:265–271CrossRefPubMed
7.
go back to reference Chen ST, Wang JP, Garey LJ, Jen LS (1999) Expression of beta amyloid precursor and Bc2-2 proto-oncogene proteins in rat retinas after intravitreal injection of aminoadipic acid. Neurochem Int 35:371–382CrossRefPubMed Chen ST, Wang JP, Garey LJ, Jen LS (1999) Expression of beta amyloid precursor and Bc2-2 proto-oncogene proteins in rat retinas after intravitreal injection of aminoadipic acid. Neurochem Int 35:371–382CrossRefPubMed
8.
go back to reference Cherry TJ, Trimarchi JM, Stadler MB, Cepko CL (2009) Development and diversification of retinal amacrine interneurons at single cell resolution. Proc Natl Acad Sci USA 106:9495–9500CrossRefPubMed Cherry TJ, Trimarchi JM, Stadler MB, Cepko CL (2009) Development and diversification of retinal amacrine interneurons at single cell resolution. Proc Natl Acad Sci USA 106:9495–9500CrossRefPubMed
9.
go back to reference Dinet V, Girard-Naud N, Voisin P, Bernard M (2006) Melatoninergic differentiation of retinal photoreceptors: activation of the chicken hydroxyindole-O-methyltransferase promoter requires a homeodomain-binding element that interacts with Otx2. Exp Eye Res 83:276–290CrossRefPubMed Dinet V, Girard-Naud N, Voisin P, Bernard M (2006) Melatoninergic differentiation of retinal photoreceptors: activation of the chicken hydroxyindole-O-methyltransferase promoter requires a homeodomain-binding element that interacts with Otx2. Exp Eye Res 83:276–290CrossRefPubMed
10.
go back to reference Ding Q, Chen H, Xie X, Libby RT, Tian N, Gan L (2009) BARHL2 differentially regulates the development of retinal amacrine and ganglion neurons. J Neurosci 29:3992–4003CrossRefPubMed Ding Q, Chen H, Xie X, Libby RT, Tian N, Gan L (2009) BARHL2 differentially regulates the development of retinal amacrine and ganglion neurons. J Neurosci 29:3992–4003CrossRefPubMed
11.
go back to reference Dyer MA, Cepko CL (2001) p27Kip1 and p57Kip2 regulate proliferation in distinct retinal progenitor cell populations. J Neurosci 21:4259–4271PubMed Dyer MA, Cepko CL (2001) p27Kip1 and p57Kip2 regulate proliferation in distinct retinal progenitor cell populations. J Neurosci 21:4259–4271PubMed
12.
go back to reference Fujitani Y, Fujitami S, Luo H et al (2006) Ptf1a determines amacrine and horizontal cell fates during mouse retinal development. Development 133:4439–4450CrossRefPubMed Fujitani Y, Fujitami S, Luo H et al (2006) Ptf1a determines amacrine and horizontal cell fates during mouse retinal development. Development 133:4439–4450CrossRefPubMed
13.
go back to reference Galli-Resta L, Ensini M (1996) An intrinsic time limit between genesis and death of individual neurons in the developing ganglion cell retinal layer. J Neurosci 16:2318–2324PubMed Galli-Resta L, Ensini M (1996) An intrinsic time limit between genesis and death of individual neurons in the developing ganglion cell retinal layer. J Neurosci 16:2318–2324PubMed
14.
go back to reference Gastinger MJ, Singh RS, Barber AJ (2006) Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic rat and Ins2Akita-diabetic mouse retinas. Invest. Ophthalmol Vis Sci 47:3143–3150CrossRefPubMed Gastinger MJ, Singh RS, Barber AJ (2006) Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic rat and Ins2Akita-diabetic mouse retinas. Invest. Ophthalmol Vis Sci 47:3143–3150CrossRefPubMed
15.
go back to reference Glotin AL, Debacq-Chainiaux F, Brossas JY et al (2008) Prematurely senescent ARPE-19 cells display features of age-related macular degeneration. Free Radic Med 44:1348–1361CrossRef Glotin AL, Debacq-Chainiaux F, Brossas JY et al (2008) Prematurely senescent ARPE-19 cells display features of age-related macular degeneration. Free Radic Med 44:1348–1361CrossRef
16.
go back to reference Hitchcock PF, Macdonald RE, VanDeRyt JT, Wilson SW (1996) Antibodies against Pax6 immunostain amacrine and ganglion cells and neuronal progenitors, but not rod precursors, in the normal and regenerating retina of the goldfish. J Neurobiol 29:399–413CrossRefPubMed Hitchcock PF, Macdonald RE, VanDeRyt JT, Wilson SW (1996) Antibodies against Pax6 immunostain amacrine and ganglion cells and neuronal progenitors, but not rod precursors, in the normal and regenerating retina of the goldfish. J Neurobiol 29:399–413CrossRefPubMed
17.
go back to reference Hoe HS, Lee KJ, Carney RS et al (2009) Interaction of reelin with amyloid precursor protein promotes neurite outgrowth. J Neurosci 29:7459CrossRefPubMed Hoe HS, Lee KJ, Carney RS et al (2009) Interaction of reelin with amyloid precursor protein promotes neurite outgrowth. J Neurosci 29:7459CrossRefPubMed
18.
go back to reference Hoe HS, Tran TS, Matsuoka Y, Howell BW, Rebeck GW (2006) DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing. J Biol Chem J Biol Chem 281:35176–35185 Hoe HS, Tran TS, Matsuoka Y, Howell BW, Rebeck GW (2006) DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing. J Biol Chem J Biol Chem 281:35176–35185
19.
go back to reference Huberman AD, Clandinin TR, Baier H (2010) Molecular and cellular mechanisms of lamina-specific axon targeting. Cold Spring Harb Perspect Biol 2:a001743CrossRefPubMed Huberman AD, Clandinin TR, Baier H (2010) Molecular and cellular mechanisms of lamina-specific axon targeting. Cold Spring Harb Perspect Biol 2:a001743CrossRefPubMed
20.
go back to reference Inoue T, Hojo M, Bessho Y, Tano Y, Lee JE, Kageyama R (2002) Math3 and NeuroD regulate amacrine cell fate specification in the retina. Development 129:831–842PubMed Inoue T, Hojo M, Bessho Y, Tano Y, Lee JE, Kageyama R (2002) Math3 and NeuroD regulate amacrine cell fate specification in the retina. Development 129:831–842PubMed
21.
go back to reference Jeon CJ, Strettoi E, Masland RH (1998) The major cell populations of the mouse retina. J Neurosci 18:8936–8946PubMed Jeon CJ, Strettoi E, Masland RH (1998) The major cell populations of the mouse retina. J Neurosci 18:8936–8946PubMed
22.
go back to reference Johnson LV, Leitner P, Rives AJ, Staples MK, Radeke MJ, Anderson DH (2002) The Alzheimer’s A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci USA 99:11830–11835CrossRefPubMed Johnson LV, Leitner P, Rives AJ, Staples MK, Radeke MJ, Anderson DH (2002) The Alzheimer’s A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci USA 99:11830–11835CrossRefPubMed
23.
go back to reference Kirazov E, Kirazov L, Bighl V, Schliebs R (2001) Ontogenetic changes in protein level of amyloid precursor protein (APP) in growth cones and synaptosomes from rat brain and prenatal expression pattern of APP mRNA isoforms in developing rat embryo. Int J Dev Neurosci 19(3):287–296CrossRefPubMed Kirazov E, Kirazov L, Bighl V, Schliebs R (2001) Ontogenetic changes in protein level of amyloid precursor protein (APP) in growth cones and synaptosomes from rat brain and prenatal expression pattern of APP mRNA isoforms in developing rat embryo. Int J Dev Neurosci 19(3):287–296CrossRefPubMed
24.
go back to reference Kolb H (1997) Amacrine cells of the mammalian retina: neurocircuitry and functional roles. Eye 11:904–923PubMed Kolb H (1997) Amacrine cells of the mammalian retina: neurocircuitry and functional roles. Eye 11:904–923PubMed
25.
go back to reference Lee EJ, Kim HJ, Lim EJ et al (2004) AII amacrine cells in the mammalian retina show disabled-1 immunoreactivity. J Comp Neurol 470:372–381CrossRefPubMed Lee EJ, Kim HJ, Lim EJ et al (2004) AII amacrine cells in the mammalian retina show disabled-1 immunoreactivity. J Comp Neurol 470:372–381CrossRefPubMed
26.
go back to reference Lillien L (1994) Neurogenesis in the vertebrate retina. Perspect Dev Neurobiol 2:175–182PubMed Lillien L (1994) Neurogenesis in the vertebrate retina. Perspect Dev Neurobiol 2:175–182PubMed
27.
go back to reference Löffler KU, Edward DP, Tso M (1995) Immunoreactivity against tau, amyloid precursor protein, and beta-amyloid in the human retina. Invest Ophthalmol Vis Sci 36:24–31PubMed Löffler KU, Edward DP, Tso M (1995) Immunoreactivity against tau, amyloid precursor protein, and beta-amyloid in the human retina. Invest Ophthalmol Vis Sci 36:24–31PubMed
28.
go back to reference Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, Chen J (2006) Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest 116:378–385CrossRefPubMed Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, Chen J (2006) Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest 116:378–385CrossRefPubMed
29.
go back to reference Magara F, Müller U, Li ZW et al (1999) Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein. Proc Natl Acad Sci USA 96:4656–4661CrossRefPubMed Magara F, Müller U, Li ZW et al (1999) Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein. Proc Natl Acad Sci USA 96:4656–4661CrossRefPubMed
30.
go back to reference Mo Z, Li S, Yang X, Xiang M (2004) Role of Barhl2 homeobox gene in the specification of glycinergic amacrine cells. Development 131:1607–1618CrossRefPubMed Mo Z, Li S, Yang X, Xiang M (2004) Role of Barhl2 homeobox gene in the specification of glycinergic amacrine cells. Development 131:1607–1618CrossRefPubMed
31.
go back to reference Nakhai H, Sel S, Favor J et al (2007) Ptf1a is essential for the differentiation of GABAergic and glycinergic amacrine cells and horizontal cells in the mouse retina. Development 134:1151–1160CrossRefPubMed Nakhai H, Sel S, Favor J et al (2007) Ptf1a is essential for the differentiation of GABAergic and glycinergic amacrine cells and horizontal cells in the mouse retina. Development 134:1151–1160CrossRefPubMed
32.
go back to reference Needham BE, Wlodek ME, Ciccotosto GD et al (2008) Identification of the Alzheimer’s disease amyloid precursor protein (APP) and its homologue APLP2 as essential modulators of glucose and insulin homeostasis and growth. J Pathol 215:155–163CrossRefPubMed Needham BE, Wlodek ME, Ciccotosto GD et al (2008) Identification of the Alzheimer’s disease amyloid precursor protein (APP) and its homologue APLP2 as essential modulators of glucose and insulin homeostasis and growth. J Pathol 215:155–163CrossRefPubMed
33.
go back to reference Nguyen-Legros J (1988) Functional neuroarchitecture of the retina: hypothesis on the dysfunction of retinal dopaminergic circuitry in Parkinson’s disease. Surg Radiol Anat 10(2):137–144CrossRefPubMed Nguyen-Legros J (1988) Functional neuroarchitecture of the retina: hypothesis on the dysfunction of retinal dopaminergic circuitry in Parkinson’s disease. Surg Radiol Anat 10(2):137–144CrossRefPubMed
34.
go back to reference Ning A, Cui JZ, To E, Hsiao Ashe K, Matsubara JA (2008) Amyloid BETA deposits lead to retinal degeneration in a mouse model of Alzheimer disease. Invest Ophthalmol Vis Sci 49:5136–5143CrossRefPubMed Ning A, Cui JZ, To E, Hsiao Ashe K, Matsubara JA (2008) Amyloid BETA deposits lead to retinal degeneration in a mouse model of Alzheimer disease. Invest Ophthalmol Vis Sci 49:5136–5143CrossRefPubMed
35.
go back to reference Offe K, Dodson SE, Shoemaker JT et al (2006) The lipoprotein receptor LR11 regulates amyloid beta production and amyloid precursor protein traffic in endosomal compartments. J Neurosci 26:1596–1603CrossRefPubMed Offe K, Dodson SE, Shoemaker JT et al (2006) The lipoprotein receptor LR11 regulates amyloid beta production and amyloid precursor protein traffic in endosomal compartments. J Neurosci 26:1596–1603CrossRefPubMed
36.
go back to reference Ohta M, Kitamoto T, Iwaki T, Ohgami T, Fukui M, Tateishi J (1993) Immunohistochemical distribution of amyloid precursor protein during normal rat development. Brain Res Dev Brain Res 75:151–161CrossRefPubMed Ohta M, Kitamoto T, Iwaki T, Ohgami T, Fukui M, Tateishi J (1993) Immunohistochemical distribution of amyloid precursor protein during normal rat development. Brain Res Dev Brain Res 75:151–161CrossRefPubMed
37.
go back to reference Osterfield M, Egelund R, Young LM, Flanagan JG (2008) Interaction of amyloid precursor protein with contactins and NgCAM in the retinotectal system. Development 135:1189–1199CrossRefPubMed Osterfield M, Egelund R, Young LM, Flanagan JG (2008) Interaction of amyloid precursor protein with contactins and NgCAM in the retinotectal system. Development 135:1189–1199CrossRefPubMed
38.
go back to reference Perez SE, Lumayag S, Kovacs B, Mufson EJ, Xu S (2008) {beta}-Amyloid deposition and functional impairment in the retina of the APPswe/PS1{Delta}E9 transgenic mouse model of Alzheimer’s disease. Invest Ophthalmol Vis Sci 50:793–800CrossRefPubMed Perez SE, Lumayag S, Kovacs B, Mufson EJ, Xu S (2008) {beta}-Amyloid deposition and functional impairment in the retina of the APPswe/PS1{Delta}E9 transgenic mouse model of Alzheimer’s disease. Invest Ophthalmol Vis Sci 50:793–800CrossRefPubMed
39.
go back to reference Rice DS, Nusinowitz S, Azimi AM, Martinez A, Soriano E, Curran T (2001) The reelin pathway modulates the structure and function of retinal synaptic circuitry. Neuron 31:929–941CrossRefPubMed Rice DS, Nusinowitz S, Azimi AM, Martinez A, Soriano E, Curran T (2001) The reelin pathway modulates the structure and function of retinal synaptic circuitry. Neuron 31:929–941CrossRefPubMed
40.
go back to reference Salbaum JM, Ruddle FH (1994) Embryonic expression pattern of amyloid protein precursor suggests a role in differentiation of specific subsets of neurons. J Exp Zool 269:116–127CrossRefPubMed Salbaum JM, Ruddle FH (1994) Embryonic expression pattern of amyloid protein precursor suggests a role in differentiation of specific subsets of neurons. J Exp Zool 269:116–127CrossRefPubMed
41.
go back to reference Seth A, Cui J, To E, Kwee M, Matsubara J (2008) Complement-associated deposits in the human retina. Invest Ophthalmol Vis Sci 49:743–750CrossRefPubMed Seth A, Cui J, To E, Kwee M, Matsubara J (2008) Complement-associated deposits in the human retina. Invest Ophthalmol Vis Sci 49:743–750CrossRefPubMed
42.
go back to reference Steinbach JP, Müller U, Leist M, Li ZW, Nicotera P, Aguzzi A (1998) Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Cell Death Differ 5:858–866CrossRefPubMed Steinbach JP, Müller U, Leist M, Li ZW, Nicotera P, Aguzzi A (1998) Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Cell Death Differ 5:858–866CrossRefPubMed
43.
go back to reference Wang B, Yang L, Wang Z, Zheng H (2007) Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc Natl Acad Sci USA 104:14140–14145CrossRefPubMed Wang B, Yang L, Wang Z, Zheng H (2007) Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc Natl Acad Sci USA 104:14140–14145CrossRefPubMed
44.
go back to reference White AR, Reyes R, Mercer JF et al (1999) Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res 842:439–444CrossRefPubMed White AR, Reyes R, Mercer JF et al (1999) Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res 842:439–444CrossRefPubMed
45.
go back to reference Wilquet V, De Strooper B (2004) Amyloid-beta precursor protein processing in neurodegeneration. Curr Opin Neurobiol 14:582–588CrossRefPubMed Wilquet V, De Strooper B (2004) Amyloid-beta precursor protein processing in neurodegeneration. Curr Opin Neurobiol 14:582–588CrossRefPubMed
46.
go back to reference Yamagata M, Sanes JR (2008) Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina. Nature 451:465–469CrossRefPubMed Yamagata M, Sanes JR (2008) Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina. Nature 451:465–469CrossRefPubMed
47.
48.
go back to reference Young-Pearse TL, Bai J, Chang R, Zheng JB, LoTurco JJ, Selkoe DJ (2007) A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. J Neurosci 27:14459–14469CrossRefPubMed Young-Pearse TL, Bai J, Chang R, Zheng JB, LoTurco JJ, Selkoe DJ (2007) A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. J Neurosci 27:14459–14469CrossRefPubMed
49.
go back to reference Young RW (1984) Cell death during differentiation of the retina in the mouse. J Comp Neurol 229:362–373CrossRefPubMed Young RW (1984) Cell death during differentiation of the retina in the mouse. J Comp Neurol 229:362–373CrossRefPubMed
50.
go back to reference Zheng H, Jiang MH, Trumbauer ME et al (1995) Beta-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81:525–531CrossRefPubMed Zheng H, Jiang MH, Trumbauer ME et al (1995) Beta-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81:525–531CrossRefPubMed
Metadata
Title
APP involvement in retinogenesis of mice
Authors
Virginie Dinet
Na An
Giuseppe D. Ciccotosto
Julien Bruban
Agathe Maoui
Shayne A. Bellingham
Andrew F. Hill
Olav M. Andersen
Anders Nykjaer
Laurent Jonet
Roberto Cappai
Frédéric Mascarelli
Publication date
01-03-2011
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 3/2011
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-010-0762-2

Other articles of this Issue 3/2011

Acta Neuropathologica 3/2011 Go to the issue