CoChat
Sign Up
Cited by 363Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationAlzheimer's disease research and treatments

The Disintegrin/Metalloproteinase ADAM10 Is Essential for the Establishment of the Brain Cortex

Open access
Jorissen, Ellen, Prox, Johannes, Bernreuther, Christian, Weber, Silvio, Schwanbeck, Ralf, Serneels, Lutgarde, Snellinx, An, Craessaerts, Katleen +8 more·2010·The Journal of Neuroscience
DOI 10.1523/jneurosci.5221-09.2010PMC PMC2921981
Open this paper in CoChat — free accountOpen PDF

Abstract

The metalloproteinase and major amyloid precursor protein (APP) α-secretase candidate ADAM10 is responsible for the shedding of proteins important for brain development, such as cadherins, ephrins, and Notch receptors.Adam10−/−mice die at embryonic day 9.5, due to major defects in development of somites and vasculogenesis. To investigate the function of ADAM10 in brain, we generated Adam10 conditional knock-out (cKO) mice using a Nestin-Cre promotor, limiting ADAM10 inactivation to neural progenitor cells (NPCs) and NPC-derived neurons and glial cells. The cKO mice die perinatally with a disrupted neocortex and a severely reduced ganglionic eminence, due to precocious neuronal differentiation resulting in an early depletion of progenitor cells. Premature neuronal differentiation is associated with aberrant neuronal migration and a disorganized laminar architecture in the neocortex. Neurospheres derived from Adam10 cKO mice have a disrupted sphere organization and segregated more neurons at the expense of astrocytes. We found that Notch-1 processing was affected, leading to downregulation of several Notch-regulated genes in Adam10 cKO brains, in accordance with the central role of ADAM10 in this signaling pathway and explaining the neurogenic phenotype. Finally, we found that α-secretase-mediated processing of APP was largely reduced in these neurons, demonstrating that ADAM10 represents the most important APP α-secretase in brain. Our study reveals that ADAM10 plays a central role in the developing brain by controlling mainly Notch-dependent pathways but likely also by reducing surface shedding of other neuronal membrane proteins including APP.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1523/jneurosci.5221-09.2010

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • GDE2 is required to control neuronal ADAM10 α-secretase activity.

    “these observations support the model that GDE2 is required to control neuronal ADAM10 α-secretase activity.”

    From GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein (2021) · cites this paper as [4]

    The Results section, “ADAM10 contributes to APP processing in primary neurons” (page unavailable), reports that ADAM10 is the most important APP α-secretase in the neurons studied. Neither that passage nor the searched passages address GDE2 or show that it is required to control ADAM10 activity. The cited paper supports ADAM10’s neuronal α-secretase role, but not the claim about GDE2. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • ADAM10 is the major α-secretase that cleaves APP in neurons.

    “genetic ablation and knockdown studies identify ADAM10 as the major α-secretase that cleaves APP in neurons (3, 4).”

    From GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein (2021) · cites this paper as [4]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 74 · Cited by 363

Research works printed but not linked: 69

  1. Alexson TO Hitoshi S Coles BL Bernstein A van der Kooy D 2006 Notch signaling is required to maintain all neural stem cell populations--irrespective of spatial or temporal niche Dev Neurosci 28 34 48 16508302
  2. Allinson TM Parkin ET Turner AJ Hooper NM 2003 ADAMs family members as amyloid precursor protein alpha-secretases J Neurosci Res 74 342 352 14598310
  3. Angevine JB Jr Sidman RL 1961 Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse Nature 192 766 768 17533671
  4. Annaert WG Levesque L Craessaerts K Dierinck I Snellings G Westaway D George-Hyslop PS Cordell B Fraser P De Strooper B 1999 Presenilin 1 controls gamma-secretase processing of amyloid precursor protein in pre-golgi compartments of hippocampal neurons J Cell Biol 147 277 294 10525535 PMC2174229
  5. Artavanis-Tsakonas S Rand MD Lake RJ 1999 Notch signaling: cell fate control and signal integration in development Science 284 770 776 10221902
  6. Asai M Hattori C Szabo B Sasagawa N Maruyama K Tanuma S Ishiura S 2003 Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase Biochem Biophys Res Commun 301 231 235 12535668
  7. Brou C Logeat F Gupta N Bessia C LeBail O Doedens JR Cumano A Roux P Black RA Israel A 2000 A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE Mol Cell 5 207 216 10882063
  8. Buxbaum JD Liu KN Luo Y Slack JL Stocking KL Peschon JJ Johnson RS Castner BJ Cerretti DP Black RA 1998 Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor J Biol Chem 273 27765 27767 9774383
  9. Cagavi Bozkulak E Weinmaster G 2009 Selective Use of Adam10 and Adam17 in Activation of Notch1 Signaling Mol Cell Biol PMC2772745 19704010
  10. Caille I Allinquant B Dupont E Bouillot C Langer A Muller U Prochiantz A 2004 Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone Development 131 2173 2181 15073156
  11. Campos LS Leone DP Relvas JB Brakebusch C Fassler R Suter U ffrench-Constant C 2004 Beta1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance Development 131 3433 3444 15226259
  12. Caviness VS Jr Takahashi T Nowakowski RS 1995 Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model Trends Neurosci 18 379 383 7482802
  13. Corbin JG Gaiano N Juliano SL Poluch S Stancik E Haydar TF 2008 Regulation of neural progenitor cell development in the nervous system J Neurochem 106 2272 2287 18819190 PMC2640107
  14. Costa RM Honjo T Silva AJ 2003 Learning and memory deficits in Notch mutant mice Curr Biol 13 1348 1354 12906797
  15. De Strooper B Saftig P Craessaerts K Vanderstichele H Guhde G Annaert W Von Figura K Van Leuven F 1998 Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein Nature 391 387 390 9450754
  16. De Strooper B Annaert W Cupers P Saftig P Craessaerts K Mumm JS Schroeter EH Schrijvers V Wolfe MS Ray WJ Goate A Kopan R 1999 A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain Nature 398 518 522 10206645
  17. Furukawa K Barger SW Blalock EM Mattson MP 1996 Activation of K+ channels and suppression of neuronal activity by secreted beta-amyloid-precursor protein Nature 379 74 78 8538744
  18. Gaiano N 2008 Strange bedfellows: Reelin and Notch signaling interact to regulate cell migration in the developing neocortex Neuron 60 189 191 18957210
  19. Gordon WR Arnett KL Blacklow SC 2008 The molecular logic of Notch signaling--a structural and biochemical perspective J Cell Sci 121 3109 3119 18799787 PMC2696053
  20. Graus-Porta D Blaess S Senften M Littlewood-Evans A Damsky C Huang Z Orban P Klein R Schittny JC Muller U 2001 Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex Neuron 31 367 379 11516395
  21. Gutwein P Mechtersheimer S Riedle S Stoeck A Gast D Joumaa S Zentgraf H Fogel M Altevogt DP 2003 ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and in released membrane vesicles Faseb J 17 292 294 12475894
  22. Hartmann D de Strooper B Serneels L Craessaerts K Herreman A Annaert W Umans L Lubke T Lena Illert A von Figura K Saftig P 2002 The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts Hum Mol Genet 11 2615 2624 12354787
  23. Hashimoto-Torii K Torii M Sarkisian MR Bartley CM Shen J Radtke F Gridley T Sestan N Rakic P 2008 Interaction between Reelin and Notch signaling regulates neuronal migration in the cerebral cortex Neuron 60 273 284 18957219 PMC2913541
  24. Hatten ME 1990 Riding the glial monorail: a common mechanism for glial-guided neuronal migration in different regions of the developing mammalian brain Trends Neurosci 13 179 184 1693236
  25. Hatten ME 1993 The role of migration in central nervous system neuronal development Curr Opin Neurobiol 3 38 44 8453287
  26. Hattori M Osterfield M Flanagan JG 2000 Regulated cleavage of a contact-mediated axon repellent Science 289 1360 1365 10958785
  27. Hinkle CL Diestel S Lieberman J Maness PF 2006 Metalloprotease-induced ectodomain shedding of neural cell adhesion molecule (NCAM) J Neurobiol 66 1378 1395 16967505
  28. Hitoshi S Alexson T Tropepe V Donoviel D Elia AJ Nye JS Conlon RA Mak TW Bernstein A van der Kooy D 2002 Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells Genes Dev 16 846 858 11937492 PMC186324
  29. Hooper NM Turner AJ 2002 The search for alpha-secretase and its potential as a therapeutic approach to Alzheimer s disease Curr Med Chem 9 1107 1119 12052175
  30. Irvin DK Zurcher SD Nguyen T Weinmaster G Kornblum HI 2001 Expression patterns of Notch1, Notch2, and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development J Comp Neurol 436 167 181 11438922
  31. Ishibashi M Ang SL Shiota K Nakanishi S Kageyama R Guillemot F 1995 Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1)leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects Genes Dev 9 3136 3148 8543157
  32. Janes PW Saha N Barton WA Kolev MV Wimmer-Kleikamp SH Nievergall E Blobel CP Himanen JP Lackmann M Nikolov DB 2005 Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans Cell 123 291 304 16239146
  33. Kim WY Shen J 2008 Presenilins are required for maintenance of neural stem cells in the developing brain Mol Neurodegener 3 2 18182109 PMC2235867
  34. Lieber T Kidd S Young MW 2002 kuzbanian-mediated cleavage of Drosophila Notch Genes Dev 16 209 221 11799064 PMC155326
  35. Lin J Luo J Redies C 2008 Differential expression of five members of the ADAM family in the developing chicken brain Neuroscience 157 360 375 18832016
  36. Lindsell CE Boulter J diSibio G Gossler A Weinmaster G 1996 Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development Mol Cell Neurosci 8 14 27 8923452
  37. Louvi A Artavanis-Tsakonas S 2006 Notch signalling in vertebrate neural development Nat Rev Neurosci 7 93 102 16429119
  38. Mathews PM Jiang Y Schmidt SD Grbovic OM Mercken M Nixon RA 2002 Calpain activity regulates the cell surface distribution of amyloid precursor protein. Inhibition of calpains enhances endosomal generation of beta-cleaved C-terminal APP fragments J Biol Chem 277 36415 36424 12087104
  39. Mattson MP 1994 Secreted forms of beta-amyloid precursor protein modulate dendrite outgrowth and calcium responses to glutamate in cultured embryonic hippocampal neurons J Neurobiol 25 439 450 7915758
  40. McConnell SK 1995 Constructing the cerebral cortex: neurogenesis and fate determination Neuron 15 761 768 7576626
  41. Mission JP Takahashi T Caviness VS Jr 1991 Ontogeny of radial and other astroglial cells in murine cerebral cortex Glia 4 138 148 1709615
  42. Mizutani K Saito T 2005 Progenitors resume generating neurons after temporary inhibition of neurogenesis by Notch activation in the mammalian cerebral cortex Development 132 1295 1304 15750183
  43. Mumm JS Kopan R 2000 Notch signaling: from the outside in Dev Biol 228 151 165 11112321
  44. Mumm JS Schroeter EH Saxena MT Griesemer A Tian X Pan DJ Ray WJ Kopan R 2000 A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1 Mol Cell 5 197 206 10882062
  45. Pan D Rubin GM 1997 Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis Cell 90 271 280 9244301
  46. Peschon JJ Slack JL Reddy P Stocking KL Sunnarborg SW Lee DC Russell WE Castner BJ Johnson RS Fitzner JN Boyce RW Nelson N Kozlosky CJ Wolfson MF Rauch CT Cerretti DP Paxton RJ March CJ Black RA 1998 An essential role for ectodomain shedding in mammalian development Science 282 1281 1284 9812885
  47. Postina R 2008 A closer look at alpha-secretase Curr Alzheimer Res 5 179 186 18393803
  48. Postina R Schroeder A Dewachter I Bohl J Schmitt U Kojro E Prinzen C Endres K Hiemke C Blessing M Flamez P Dequenne A Godaux E van Leuven F Fahrenholz F 2004 A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model J Clin Invest 113 1456 1464 15146243 PMC406531
  49. Reiss K Maretzky T Ludwig A Tousseyn T de Strooper B Hartmann D Saftig P 2005 ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling Embo J 24 742 752 15692570 PMC549617
  50. Reynolds BA Weiss S 1996 Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell Dev Biol 175 1 13 8608856
  51. Reynolds BA Tetzlaff W Weiss S 1992 A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes J Neurosci 12 4565 4574 1432110 PMC6575989
  52. Rohe M Carlo AS Breyhan H Sporbert A Militz D Schmidt V Wozny C Harmeier A Erdmann B Bales KR Wolf S Kempermann G Paul SM Schmitz D Bayer TA Willnow TE Andersen OM 2008 Sortilin-related receptor with A-type repeats (SORLA)affects the amyloid precursor protein-dependent stimulation of ERK signaling and adult neurogenesis J Biol Chem 283 14826 14834 18362153
  53. Schuurmans C Guillemot F 2002 Molecular mechanisms underlying cell fate specification in the developing telencephalon Curr Opin Neurobiol 12 26 34 11861161
  54. Skovronsky DM Moore DB Milla ME Doms RW Lee VM 2000 Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network J Biol Chem 275 2568 2575 10644715
  55. Tronche F Kellendonk C Kretz O Gass P Anlag K Orban PC Bock R Klein R Schutz G 1999 Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety Nat Genet 23 99 103 10471508
  56. Tropepe V Sibilia M Ciruna BG Rossant J Wagner EF van der Kooy D 1999 Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon Dev Biol 208 166 188 10075850
  57. van Tetering G van Diest P Verlaan I van der Wall E Kopan R Vooijs M 2009 The metalloprotease ADAM10 is required for notch1 S2 cleavage J Biol Chem PMC2781502 19726682
  58. Vandermeeren M Geraerts M Pype S Dillen L Van Hove C Mercken M 2001 The functional gamma-secretase inhibitor prevents production of amyloid beta 1-34 in human and murine cell lines Neurosci Lett 315 145 148 11716984
  59. Vincent B 2004 ADAM proteases: protective role in Alzheimer’s and prion diseases? Curr Alzheimer Res 1 165 174 15975064
  60. Wang Y Chan SL Miele L Yao PJ Mackes J Ingram DK Mattson MP Furukawa K 2004 Involvement of Notch signaling in hippocampal synaptic plasticity Proc Natl Acad Sci U S A 101 9458 9462 15190179 PMC438998
  61. Wen C Metzstein MM Greenwald I 1997 SUP-17, a Caenorhabditis elegans ADAM protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling Development 124 4759 4767 9428412
  62. Wiltfang J Esselmann H Bibl M Smirnov A Otto M Paul S Schmidt B Klafki HW Maler M Dyrks T Bienert M Beyermann M Ruther E Kornhuber J 2002 Highly conserved and disease-specific patterns of carboxyterminally truncated Abeta peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer’s disease and in patients with chronic neuroinflammation J Neurochem 81 481 496 12065657
  63. Yang X Klein R Tian X Cheng HT Kopan R Shen J 2004 Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway Dev Biol 269 81 94 15081359
  64. Yoon K Gaiano N 2005 Notch signaling in the mammalian central nervous system: insights from mouse mutants Nat Neurosci 8 709 715 15917835
  65. Yoon K Nery S Rutlin ML Radtke F Fishell G Gaiano N 2004 Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in telencephalic progenitors J Neurosci 24 9497 9506 15509736 PMC6730142
  66. Yu H Saura CA Choi SY Sun LD Yang X Handler M Kawarabayashi T Younkin L Fedeles B Wilson MA Younkin S Kandel ER Kirkwood A Shen J 2001 APP processing and synaptic plasticity in presenilin-1 conditional knockout mice Neuron 31 713 726 11567612
  67. Yun K Fischman S Johnson J Hrabe de Angelis M Weinmaster G Rubenstein JL 2002 Modulation of the notch signaling by Mash1 and Dlx1/2 regulates sequential specification and differentiation of progenitor cell types in the subcortical telencephalon Development 129 5029 5040 12397111
  68. Zhong W Jiang MM Weinmaster G Jan LY Jan YN 1997 Differential expression of mammalian Numb, Numblike and Notch1 suggests distinct roles during mouse cortical neurogenesis Development 124 1887 1897 9169836
  69. Zimmerman L Parr B Lendahl U Cunningham M McKay R Gavin B Mann J Vassileva G McMahon A 1994 Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors Neuron 12 11 24 8292356

Authors
Jorissen, E., Prox, J., Bernreuther, C., Weber, S., Schwanbeck, R., Serneels, L., Snellinx, A., Craessaerts, K., Thathiah, A., Tesseur, I., Bartsch, U., Weskamp, G., Blobel, C. P., Glatzel, M., De Strooper, B., & Saftig, P.
Affiliations
  • Vlaams Instituut voor Biotechnologie (BE)
  • Christian-Albrechts-Universität zu Kiel (DE)
  • University Medical Center Hamburg-Eppendorf (DE)
  • Hospital for Special Surgery (US)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2010-04-06
Volume
30
Issue
14
Pages
4833-4844
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.5221-09.2010
PMC
PMC2921981
OpenAlex
W2040170596
Cited by
363
References
74
Citations by year
2026: 2 · 2025: 8 · 2024: 16 · 2023: 21 · 2022: 21 · 2021: 21 · 2020: 18 · 2019: 27 · 2018: 22 · 2017: 21 · 2016: 24 · 2015: 26 · 2014: 28 · 2013: 31 · 2012: 31
FWCI
10.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Lirias (submittedVersion)
Funders
  • European Molecular Biology Organization
  • Deutsche Forschungsgemeinschaft
  • Belgian Federal Science Policy Office
  • Vlaams Instituut voor Biotechnologie
  • Exzellenzclusters Entzündungsforschung
  • Vlaamse regering
  • National Institutes of Health
  • National Eye Institute (EY015719, R01EY015719)
  • National Institute of General Medical Sciences (R01GM064750, GM-64750)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
ADAM10, amyloid precursor protein, alpha-secretase, Notch signaling, neocortex development, ganglionic eminence, neural progenitor cells, neuronal migration, conditional knockout mice, neurospheres, astrocytes, brain development
MeSH terms
ADAM10 Protein, Animals, Animals, Newborn, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Female, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Pregnancy, Amyloid beta-Protein Precursor, Mice, Knockout, Cell Proliferation, Mice, ADAM Proteins, Receptors, Notch, Amyloid Precursor Protein Secretases, Neurogenesis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review