Schizophrenia-related microdeletion causes defective ciliary motility and brain ventricle enlargement via microRNA-dependent mechanisms in mice.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 02 2020
14 02 2020
Historique:
received:
17
06
2019
accepted:
22
01
2020
entrez:
16
2
2020
pubmed:
16
2
2020
medline:
2
6
2020
Statut:
epublish
Résumé
Progressive ventricular enlargement, a key feature of several neurologic and psychiatric diseases, is mediated by unknown mechanisms. Here, using murine models of 22q11-deletion syndrome (22q11DS), which is associated with schizophrenia in humans, we found progressive enlargement of lateral and third ventricles and deceleration of ciliary beating on ependymal cells lining the ventricular walls. The cilia-beating deficit observed in brain slices and in vivo is caused by elevated levels of dopamine receptors (Drd1), which are expressed in motile cilia. Haploinsufficiency of the microRNA-processing gene Dgcr8 results in Drd1 elevation, which is brought about by a reduction in Drd1-targeting microRNAs miR-382-3p and miR-674-3p. Replenishing either microRNA in 22q11DS mice normalizes ciliary beating and ventricular size. Knocking down the microRNAs or deleting their seed sites on Drd1 mimicked the cilia-beating and ventricular deficits. These results suggest that the Dgcr8-miR-382-3p/miR-674-3p-Drd1 mechanism contributes to deceleration of ciliary motility and age-dependent ventricular enlargement in 22q11DS.
Identifiants
pubmed: 32060266
doi: 10.1038/s41467-020-14628-y
pii: 10.1038/s41467-020-14628-y
pmc: PMC7021727
doi:
Substances chimiques
Dgcr8 protein, mouse
0
MIRN674 microRNA, mouse
0
MicroRNAs
0
RNA-Binding Proteins
0
Receptors, Dopamine
0
microRNA 382, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
912Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC012833
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH097742
Pays : United States
Références
Mak, E. et al. Longitudinal whole-brain atrophy and ventricular enlargement in nondemented Parkinson’s disease. Neurobiol. Aging 55, 78–90 (2017).
pubmed: 28431288
pmcid: 5454799
doi: 10.1016/j.neurobiolaging.2017.03.012
Nestor, S. M. et al. Ventricular enlargement as a possible measure of Alzheimer’s disease progression validated using the Alzheimer’s disease neuroimaging initiative database. Brain 131, 2443–2454 (2008).
pubmed: 18669512
pmcid: 2724905
doi: 10.1093/brain/awn146
Kuller, L. H. et al. Determinants of vascular dementia in the Cardiovascular Health Cognition Study. Neurology 64, 1548–1552 (2005).
pubmed: 15883315
pmcid: 3378359
doi: 10.1212/01.WNL.0000160115.55756.DE
Kempton, M. J., Geddes, J. R., Ettinger, U., Williams, S. C. R. & Grasby, P. M. Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder. Arch. Gen. Psychiatry 65, 1017–1032 (2008).
pubmed: 18762588
doi: 10.1001/archpsyc.65.9.1017
pmcid: 18762588
Vojinovic, D. et al. Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume. Nat. Commun. 9, 3945 (2018).
pubmed: 30258056
pmcid: 6158214
doi: 10.1038/s41467-018-06234-w
Apostolova, L. G. et al. Hippocampal Atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and Alzheimer Disease. Alzheimer Dis. Assoc. Disord. 26, 17–27 (2012).
pubmed: 22343374
pmcid: 3286134
doi: 10.1097/WAD.0b013e3182163b62
Long, X. et al. Healthy aging. Acad. Radiol. 19, 785–793 (2012).
pubmed: 22503890
doi: 10.1016/j.acra.2012.03.006
pmcid: 22503890
Carmichael, O. T. et al. Ventricular volume and dementia progression in the Cardiovascular Health Study. Neurobiol. Aging 28, 389–397 (2007).
pubmed: 16504345
doi: 10.1016/j.neurobiolaging.2006.01.006
pmcid: 16504345
Johnstone, E. C., Crow, T. J., Frith, C. D., Husband, J. & Kreel, L. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 2, 924–926 (1976).
pubmed: 62160
doi: 10.1016/S0140-6736(76)90890-4
pmcid: 62160
Lawrie, S. M. & Abukmeil, S. S. Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. Br. J. Psychiatry 172, 110–120 (1998).
pubmed: 9519062
doi: 10.1192/bjp.172.2.110
pmcid: 9519062
Franke, B. et al. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nat. Neurosci. 19, 420–431 (2016).
pubmed: 26854805
pmcid: 4852730
doi: 10.1038/nn.4228
Wright, I. C. et al. Meta-analysis of regional brain volumes in schizophrenia. Am. J. Psychiatry 157, 16–25 (2000).
pubmed: 10618008
doi: 10.1176/ajp.157.1.16
pmcid: 10618008
Shenton, M. E., Dickey, C. C., Frumin, M. & McCarley, R. W. A review of MRI findings in schizophrenia. Schizophr. Res. 49, 1–52 (2001).
pubmed: 11343862
pmcid: 2812015
doi: 10.1016/S0920-9964(01)00163-3
Kempton, M. J., Stahl, D., Williams, S. C. & DeLisi, L. E. Progressive lateral ventricular enlargement in schizophrenia: a meta-analysis of longitudinal MRI studies. Schizophr. Res. 120, 54–62 (2010).
pubmed: 20537866
doi: 10.1016/j.schres.2010.03.036
pmcid: 20537866
van Erp, T. G. et al. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol. Psychiatry 21, 585 (2016).
pubmed: 26283641
doi: 10.1038/mp.2015.118
pmcid: 26283641
Styner, M. et al. Morphometric analysis of lateral ventricles in schizophrenia and healthy controls regarding genetic and disease-specific factors. Proc. Natl Acad. Sci. USA 102, 4872–4877 (2005).
pubmed: 15772166
doi: 10.1073/pnas.0501117102
pmcid: 15772166
Steen, R. G., Mull, C., McClure, R., Hamer, R. M. & Lieberman, J. A. Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. Br. J. Psychiatry 188, 510–518 (2006).
pubmed: 16738340
doi: 10.1192/bjp.188.6.510
pmcid: 16738340
Vita, A. et al. Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonance imaging studies. Schizophr. Res. 82, 75–88 (2006).
pubmed: 16377156
doi: 10.1016/j.schres.2005.11.004
pmcid: 16377156
Schneider, M. et al. Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome. Am. J. Psychiatry 171, 627–639 (2014).
pubmed: 24577245
pmcid: 4285461
doi: 10.1176/appi.ajp.2013.13070864
Robin, N. H. & Shprintzen, R. J. Defining the Clinical Spectrum of Deletion 22q11.2. J. Pediatr. 147, 90–96 (2005).
pubmed: 16027702
doi: 10.1016/j.jpeds.2005.03.007
Motahari, Z., Moody, S. A., Maynard, T. M. & LaMantia, A.-S. In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? J. Neurodev. Disord. 11, 7 (2019).
pubmed: 31174463
pmcid: 6554986
doi: 10.1186/s11689-019-9267-z
Niklasson, L., Rasmussen, P., Óskarsdóttir, S. & Gillberg, C. Autism, ADHD, mental retardation and behavior problems in 100 individuals with 22q11 deletion syndrome. Res. Dev. Disabil. 30, 763–773 (2009).
pubmed: 19070990
doi: 10.1016/j.ridd.2008.10.007
Fine, S. E. et al. Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome. J. Autism Dev. Disord. 35, 461–470 (2005).
pubmed: 16134031
pmcid: 2814423
doi: 10.1007/s10803-005-5036-9
Antshel, K. M. et al. Autistic spectrum disorders in velo-cardio Facial Syndrome (22q11.2 Deletion). J. Autism Dev. Disord. 37, 1776–1786 (2007).
pubmed: 17180713
doi: 10.1007/s10803-006-0308-6
Kates, W. R. et al. Comparing phenotypes in patients with idiopathic autism to patients with velocardiofacial syndrome (22q11 DS) with and without autism. Am. J. Med. Genet. A 143A, 2642–2650 (2007).
pubmed: 17937445
doi: 10.1002/ajmg.a.32012
Finlayson, K., Butcher, S. P., Sharkey, J. & Olverman, H. J. Detection of adenosine receptor antagonists in rat brain using a modified radioreceptor assay. J. Neurosci. Methods 77, 135–142 (1997).
pubmed: 9489889
doi: 10.1016/S0165-0270(97)00118-0
Butcher, N. J. et al. Neuroimaging and clinical features in adults with a 22q11.2 deletion at risk of Parkinson’s disease. Brain 140, 1371–1383 (2017).
pubmed: 28369257
doi: 10.1093/brain/awx053
Gothelf, D. et al. Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome. Schizophr. Res. 35, 105–112 (1999).
pubmed: 9988847
doi: 10.1016/S0920-9964(98)00114-5
Green, T. et al. Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. J. Am. Acad. Child Adolesc. Psychiatry 48, 1060–1068 (2009).
pubmed: 19797984
doi: 10.1097/CHI.0b013e3181b76683
Murphy, K. C., Jones, L. A. & Owen, M. J. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch. Gen. Psychiatry 56, 940–945 (1999).
pubmed: 10530637
doi: 10.1001/archpsyc.56.10.940
pmcid: 10530637
Pulver, A. E. et al. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J. Nerv. Ment. Dis. 182, 476–478 (1994).
pubmed: 8040660
doi: 10.1097/00005053-199408000-00010
pmcid: 8040660
Shprintzen, R. J., Goldberg, R., Golding-Kushner, K. J. & Marion, R. W. Late-onset psychosis in the velo-cardio-facial syndrome. Am. J. Med. Genet. 42, 141–142 (1992).
pubmed: 1308357
doi: 10.1002/ajmg.1320420131
pmcid: 1308357
Bassett, A. S. & Chow, E. W. 22q11 deletion syndrome: a genetic subtype of schizophrenia. Biol. Psychiatry 46, 882–891 (1999).
pubmed: 10509171
pmcid: 3276595
doi: 10.1016/S0006-3223(99)00114-6
Murphy, K. C. Schizophrenia and velo-cardio-facial syndrome. Lancet 359, 426–430 (2002).
pubmed: 11844533
doi: 10.1016/S0140-6736(02)07604-3
pmcid: 11844533
Bassett, A. S. et al. Clinically detectable copy number variations in a Canadian catchment population of schizophrenia. J. Psychiatr. Res. 44, 1005–1009 (2010).
pubmed: 20643418
pmcid: 3129333
doi: 10.1016/j.jpsychires.2010.06.013
McDonald-McGinn, D. M. et al. 22q11.2 deletion syndrome. Nat. Rev. Dis. Primer 1, 15071 (2015).
doi: 10.1038/nrdp.2015.71
Chow, E. W., Watson, M., Young, D. A. & Bassett, A. S. Neurocognitive profile in 22q11 deletion syndrome and schizophrenia. Schizophr. Res. 87, 270–278 (2006).
pubmed: 16753283
pmcid: 3127863
doi: 10.1016/j.schres.2006.04.007
Karayiorgou, M., Simon, T. J. & Gogos, J. A. 22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. Nat. Rev. Neurosci. 11, 402–416 (2010).
pubmed: 20485365
pmcid: 2977984
doi: 10.1038/nrn2841
Simon, T. J. et al. Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study. Neuroimage 25, 169–180 (2005).
pubmed: 15734353
doi: 10.1016/j.neuroimage.2004.11.018
pmcid: 15734353
Chow, E. W. et al. Qualitative MRI findings in adults with 22q11 deletion syndrome and schizophrenia. Biol. Psychiatry 46, 1436–1442 (1999).
pubmed: 10578458
pmcid: 3276598
doi: 10.1016/S0006-3223(99)00150-X
Chow, E. W., Zipursky, R. B., Mikulis, D. J. & Bassett, A. S. Structural brain abnormalities in patients with schizophrenia and 22q11 deletion syndrome. Biol. Psychiatry 51, 208–215 (2002).
pubmed: 11839363
pmcid: 3295830
doi: 10.1016/S0006-3223(01)01246-X
Eliez, S., Schmitt, J. E., White, C. D. & Reiss, A. L. Children and adolescents with velocardiofacial syndrome: a volumetric MRI study. Am. J. Psychiatry 157, 409–415 (2000).
pubmed: 10698817
doi: 10.1176/appi.ajp.157.3.409
pmcid: 10698817
Campbell, L. E. et al. Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study. Brain 129, 1218–1228 (2006).
pubmed: 16569671
doi: 10.1093/brain/awl066
pmcid: 16569671
Machado, A. M. C. et al. Corpus callosum morphology and ventricular size in chromosome 22q11.2 deletion syndrome. Brain Res. 1131, 197–210 (2007).
pubmed: 17169351
doi: 10.1016/j.brainres.2006.10.082
pmcid: 17169351
Sztriha, L. et al. Clinical, MRI, and pathological features of polymicrogyria in chromosome 22q11 deletion syndrome. Am. J. Med. Genet. A 127A, 313–317 (2004).
pubmed: 15150787
doi: 10.1002/ajmg.a.30014
pmcid: 15150787
Ellegood, J. et al. Neuroanatomical phenotypes in a mouse model of the 22q11.2 microdeletion. Mol. Psychiatry 19, 99–107 (2014).
pubmed: 23999526
doi: 10.1038/mp.2013.112
pmcid: 23999526
Chun, S. et al. Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models. Science 344, 1178–1182 (2014).
pubmed: 24904170
pmcid: 4349506
doi: 10.1126/science.1253895
Chun, S. et al. Thalamic miR-338-3p mediates auditory thalamocortical disruption and its late onset in models of 22q11.2 microdeletion. Nat. Med. 23, 39–48 (2017).
pubmed: 27892953
doi: 10.1038/nm.4240
pmcid: 27892953
Earls, L. R. et al. Age-dependent microRNA control of synaptic plasticity in 22q11 deletion syndrome and schizophrenia. J. Neurosci. 32, 14132–14144 (2012).
pubmed: 23055483
doi: 10.1523/JNEUROSCI.1312-12.2012
pmcid: 23055483
Eom, T. Y., Bayazitov, I. T., Anderson, K., Yu, J. & Zakharenko, S. S. Schizophrenia-related microdeletion impairs emotional memory through microrna-dependent disruption of thalamic inputs to the amygdala. Cell Rep. 19, 1532–1544 (2017).
pubmed: 28538174
pmcid: 5457478
doi: 10.1016/j.celrep.2017.05.002
Stark, K. L. et al. Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat. Genet. 40, 751–760 (2008).
pubmed: 18469815
doi: 10.1038/ng.138
pmcid: 18469815
Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009).
pubmed: 19167326
pmcid: 19167326
doi: 10.1016/j.cell.2009.01.002
Lindsay, E. A. et al. Congenital heart disease in mice deficient for the DiGeorge syndrome region. Nature 401, 379–383 (1999).
pubmed: 10517636
pmcid: 10517636
Bassett, A. S. et al. The schizophrenia phenotype in 22q11 deletion syndrome. Am. J. Psychiatry 160, 1580–1586 (2003).
pubmed: 12944331
pmcid: 3276594
doi: 10.1176/appi.ajp.160.9.1580
Mueser, K. T. & McGurk, S. R. Schizophrenia. Lancet 363, 2063–2072 (2004).
pubmed: 15207959
doi: 10.1016/S0140-6736(04)16458-1
pmcid: 15207959
Flurkey, K., Currer, J. M. & Harrison, D. E. in The Mouse in Biomedical Research (eds Fox, J. G. & Al., E.) 637–672 American College Laboratory Animal Medicine (Elsevier, 2007).
Wang, Y., Medvid, R., Melton, C., Jaenisch, R. & Blelloch, R. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat. Genet. 39, 380–385 (2007).
pubmed: 17259983
pmcid: 3008549
doi: 10.1038/ng1969
Zhang, Y. et al. A transgenic FOXJ1-Cre system for gene inactivation in ciliated epithelial cells. Am. J. Respir. Cell Mol. Biol. 36, 515–519 (2007).
pubmed: 17255554
pmcid: 1899335
doi: 10.1165/rcmb.2006-0475RC
Delling, M., DeCaen, P. G., Doerner, J. F., Febvay, S. & Clapham, D. E. Primary cilia are specialized calcium signalling organelles. Nature 504, 311–314 (2013).
pubmed: 24336288
pmcid: 4112737
doi: 10.1038/nature12833
Mirzadeh, Z., Han, Y. G., Soriano-Navarro, M., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Cilia organize ependymal planar polarity. J. Neurosci. 30, 2600–2610 (2010).
pubmed: 20164345
pmcid: 2873868
doi: 10.1523/JNEUROSCI.3744-09.2010
Bayly, R. & Axelrod, J. D. Pointing in the right direction: new developments in the field of planar cell polarity. Nat. Rev. Genet. 12, 385–391 (2011).
pubmed: 21502960
pmcid: 4854751
doi: 10.1038/nrg2956
Guirao, B. et al. Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia. Nat. Cell Biol. 12, 341–350 (2010).
pubmed: 20305650
doi: 10.1038/ncb2040
pmcid: 20305650
Hirota, Y. et al. Planar polarity of multiciliated ependymal cells involves the anterior migration of basal bodies regulated by non-muscle myosin II. Development 137, 3037–3046 (2010).
pubmed: 20685736
doi: 10.1242/dev.050120
pmcid: 20685736
Ohata, S. et al. Loss of Dishevelleds disrupts planar polarity in ependymal motile cilia and results in hydrocephalus. Neuron 83, 558–571 (2014).
pubmed: 25043421
pmcid: 4126882
doi: 10.1016/j.neuron.2014.06.022
Tissir, F. & Goffinet, A. M. Shaping the nervous system: role of the core planar cell polarity genes. Nat. Rev. Neurosci. 14, 525–535 (2013).
pubmed: 23839596
doi: 10.1038/nrn3525
pmcid: 23839596
Wallingford, J. B. Planar cell polarity signaling, cilia and polarized ciliary beating. Curr. Opin. Cell Biol. 22, 597–604 (2010).
pubmed: 20817501
pmcid: 2974441
doi: 10.1016/j.ceb.2010.07.011
Tome, M., Moreira, E., Perez-Figares, J. M. & Jimenez, A. J. Presence of D1- and D2-like dopamine receptors in the rat, mouse and bovine multiciliated ependyma. J. Neural Transm. 114, 983–994 (2007).
pubmed: 17458496
doi: 10.1007/s00702-007-0666-z
pmcid: 17458496
Howard, S. et al. Postnatal localization and morphogenesis of cells expressing the dopaminergic D2 receptor gene in rat brain: expression in non-neuronal cells. J. Comp. Neurol. 391, 87–98 (1998).
pubmed: 9527544
doi: 10.1002/(SICI)1096-9861(19980202)391:1<87::AID-CNE8>3.0.CO;2-N
pmcid: 9527544
Hoglinger, G. U. et al. Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat. Neurosci. 7, 726–735 (2004).
pubmed: 15195095
doi: 10.1038/nn1265
pmcid: 15195095
Yamazaki, Y., Hirai, Y., Miyake, K. & Shimada, T. Targeted gene transfer into ependymal cells through intraventricular injection of AAV1 vector and long-term enzyme replacement via the CSF. Sci. Rep. 4, 5506 (2014).
pubmed: 24981028
pmcid: 4076682
doi: 10.1038/srep05506
Kahle, K. T., Kulkarni, A. V., Limbrick, D. D. & Warf, B. C. Hydrocephalus in children. Lancet 387, 788–799 (2016).
pubmed: 26256071
doi: 10.1016/S0140-6736(15)60694-8
pmcid: 26256071
Lee, L. Riding the wave of ependymal cilia: genetic susceptibility to hydrocephalus in primary ciliary dyskinesia. J. Neurosci. Res. 91, 1117–1132 (2013).
pubmed: 23686703
doi: 10.1002/jnr.23238
pmcid: 23686703
Vogel, P. et al. Congenital hydrocephalus in genetically engineered mice. Vet. Pathol. 49, 166–181 (2012).
pubmed: 21746835
doi: 10.1177/0300985811415708
pmcid: 21746835
Pfefferbaum, A., Sullivan, E. V. & Carmelli, D. Morphological changes in aging brain structures are differentially affected by time-linked environmental influences despite strong genetic stability. Neurobiol. Aging 25, 175–183 (2004).
pubmed: 14749135
doi: 10.1016/S0197-4580(03)00045-9
pmcid: 14749135
Kuller, L. H., Lopez, O. L., Becker, J. T., Chang, Y. & Newman, A. B. Risk of dementia and death in the long-term follow-up of the Pittsburgh Cardiovascular Health Study–Cognition Study. Alzheimer’s Dement. 12, 170–183 (2016).
doi: 10.1016/j.jalz.2015.08.165
van Erp, T. G. et al. A multi-scanner study of subcortical brain volume abnormalities in schizophrenia. Psychiatry Res. 222, 10–16 (2014).
pubmed: 24650452
pmcid: 4059082
doi: 10.1016/j.pscychresns.2014.02.011
Brugger, S. P. & Howes, O. D. Heterogeneity and homogeneity of regional brain structure in schizophrenia: a meta-analysis. JAMA Psychiatry 74, 1104–1111 (2017).
pubmed: 28973084
pmcid: 5669456
doi: 10.1001/jamapsychiatry.2017.2663
El Ahmadieh, T. Y. et al. Lumbar drain trial outcomes of normal pressure hydrocephalus: a single-center experience of 254 patients. J. Neurosurg. https://doi.org/10.3171/2018.8.JNS181059 (2019).
doi: 10.3171/2018.8.JNS181059
Wu, E. M. et al. Ventriculoperitoneal shunt outcomes of normal pressure hydrocephalus: a case series of 116 patients. Cureus 11, e4170 (2019).
pubmed: 31093469
pmcid: 6502283
Toma, A. K., Papadopoulos, M. C., Stapleton, S., Kitchen, N. D. & Watkins, L. D. Systematic review of the outcome of shunt surgery in idiopathic normal-pressure hydrocephalus. Acta Neurochir. 155, 1977–1980 (2013).
pubmed: 23975646
doi: 10.1007/s00701-013-1835-5
pmcid: 23975646
Tan, G. M., Arnone, D., McIntosh, A. M. & Ebmeier, K. P. Meta-analysis of magnetic resonance imaging studies in chromosome 22q11.2 deletion syndrome (velocardiofacial syndrome). Schizophr. Res. 115, 173–181 (2009).
pubmed: 19819113
doi: 10.1016/j.schres.2009.09.010
pmcid: 19819113
Zhan, L. et al. Baseline connectome modular abnormalities in the childhood phase of a longitudinal study on individuals with chromosome 22q11.2 deletion syndrome. Hum. Brain Mapp. 39, 232–248 (2018).
pubmed: 28990258
doi: 10.1002/hbm.23838
pmcid: 28990258
Tissir, F. et al. Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus. Nat. Neurosci. 13, 700–707 (2010).
pubmed: 20473291
doi: 10.1038/nn.2555
pmcid: 20473291
Ibañez-Tallon, I. et al. Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation. Hum. Mol. Genet. 13, 2133–2141 (2004).
pubmed: 15269178
doi: 10.1093/hmg/ddh219
pmcid: 15269178
Banizs, B. et al. Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development 132, 5329–5339 (2005).
pubmed: 16284123
doi: 10.1242/dev.02153
pmcid: 16284123
Vita, A. et al. A review of MRI findings in schizophrenia. Schizophr. Res. 21, 420–431 (2016).
Lattke, M., Magnutzki, A., Walther, P., Wirth, T. & Baumann, B. Nuclear factor B activation impairs ependymal ciliogenesis and links neuroinflammation to hydrocephalus formation. J. Neurosci. 32, 11511–11523 (2012).
pubmed: 22915098
pmcid: 6703776
doi: 10.1523/JNEUROSCI.0182-12.2012
Ouchi, Y. et al. Reduced adult hippocampal neurogenesis and working memory deficits in the Dgcr8-deficient mouse model of 22q11.2 deletion-associated schizophrenia can be rescued by IGF2. J. Neurosci. 33, 9408–9419 (2013).
pubmed: 23719809
pmcid: 6618567
doi: 10.1523/JNEUROSCI.2700-12.2013
Fenelon, K. et al. Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex. Proc. Natl Acad. Sci. USA 108, 4447–4452 (2011).
pubmed: 21368174
doi: 10.1073/pnas.1101219108
pmcid: 21368174
Marinaro, F. et al. MicroRNA‐independent functions of DGCR8 are essential for neocortical development and TBR1 expression. EMBO Rep. 18, 603–618 (2017).
pubmed: 28232627
pmcid: 5376964
doi: 10.15252/embr.201642800
Praveen, K., Davis, E. E. & Katsanis, N. Unique among ciliopathies: primary ciliary dyskinesia, a motile cilia disorder. F1000Prime Rep. 7, 36 (2015).
pubmed: 25926987
pmcid: 4371376
doi: 10.12703/P7-36
De Santi, M. M., Magni, A., Valletta, E. A., Gardi, C. & Lungarella, G. Hydrocephalus, bronchiectasis, and ciliary aplasia. Arch. Dis. Child. 65, 543–544 (1990).
pubmed: 2357097
pmcid: 1792142
doi: 10.1136/adc.65.5.543
Kosaki, K. et al. Absent inner dynein arms in a fetus with familial hydrocephalus-situs abnormality. Am. J. Med. Genet. 129A, 308–311 (2004).
pubmed: 15326634
doi: 10.1002/ajmg.a.30177
pmcid: 15326634
Greenstone, M. A., Jones, R. W., Dewar, A., Neville, B. G. & Cole, P. J. Hydrocephalus and primary ciliary dyskinesia. Arch. Dis. Child. 59, 481–482 (1984).
pubmed: 6732280
pmcid: 1628510
doi: 10.1136/adc.59.5.481
Conductier, G. et al. Melanin-concentrating hormone regulates beat frequency of ependymal cilia and ventricular volume. Nat. Neurosci. 16, 845–847 (2013).
pubmed: 23708141
doi: 10.1038/nn.3401
pmcid: 23708141
Satir, P. & Christensen, S. T. Overview of structure and function of mammalian cilia. Annu. Rev. Physiol. 69, 377–400 (2007).
pubmed: 17009929
doi: 10.1146/annurev.physiol.69.040705.141236
pmcid: 17009929
Salathe, M. Regulation of mammalian ciliary beating. Annu. Rev. Physiol. 69, 401–422 (2007).
pubmed: 16945069
doi: 10.1146/annurev.physiol.69.040705.141253
pmcid: 16945069
Gregory, R. I. et al. The Microprocessor complex mediates the genesis of microRNAs. Nature 432, 235–240 (2004).
pubmed: 15531877
doi: 10.1038/nature03120
pmcid: 15531877
Denli, A. M., Tops, B. B. J., Plasterk, R. H. A., Ketting, R. F. & Hannon, G. J. Processing of primary microRNAs by the Microprocessor complex. Nature 432, 231–235 (2004).
pubmed: 15531879
doi: 10.1038/nature03049
pmcid: 15531879
Horga, G. et al. Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia. Eur. Arch. Psychiatry Clin. Neurosci. 261, 467–476 (2011).
pubmed: 21431919
pmcid: 3182327
doi: 10.1007/s00406-011-0202-x
Mukherjee, A., Carvalho, F., Eliez, S. & Caroni, P. Long-lasting rescue of network and cognitive dysfunction in a genetic schizophrenia model. Cell 178, 1387–1402.e14 (2019).
pubmed: 31474363
doi: 10.1016/j.cell.2019.07.023
Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140 (2010).
pubmed: 20023653
doi: 10.1038/nn.2467
Ann Ellis, E. Solutions to the problem of substitution of ERL 4221 for vinyl cyclohexene dioxide in spurr low viscosity embedding formulations. Microsc. Today 14, 32–33 (2006).
doi: 10.1017/S1551929500050252
Lowe, D. G. & G., D. Distinctive image features from scale-invariant keypoints. Int. J. Comput. Vis. 60, 91–110 (2004).
doi: 10.1023/B:VISI.0000029664.99615.94
Felzenszwalb, P. F., Girshick, R. B., McAllester, D. & Ramanan, D. Object detection with discriminatively trained part-based models. IEEE Trans. Pattern Anal. Mach. Intell. 32, 1627–1645 (2010).
pubmed: 20634557
doi: 10.1109/TPAMI.2009.167
Jain, A. K., Murty, M. N. & Flynn, P. J. Data clustering: a review. ACM Comput. Surv. 31, 264–323 (1999).
doi: 10.1145/331499.331504
Comaniciu, D., Ramesh, V. & Meer, P. Kernel-based object tracking. IEEE Trans. Pattern Anal. Mach. Intell. 25, 564–577 (2003).
doi: 10.1109/TPAMI.2003.1195991
Christensen, M., Larsen, L. A., Kauppinen, S. & Schratt, G. Recombinant adeno-associated virus-mediated microrna delivery into the postnatal mouse brain reveals a role for miR-134 in dendritogenesis in vivo. Front. Neural Circuits 3, 16 (2010).
pubmed: 20126250
pmcid: 2809579
Mirzadeh, Z., Doetsch, F., Sawamoto, K., Wichterle, H. & Alvarez-Buylla, A. The subventricular zone en-face: wholemount staining and ependymal flow. J. Vis. Exp. https://doi.org/10.3791/1938 (2010).