Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
22 Aug 2024
Historique:
received: 09 08 2023
accepted: 23 07 2024
medline: 23 8 2024
pubmed: 23 8 2024
entrez: 22 8 2024
Statut: epublish

Résumé

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state, ultimately shortening the period of neurogenesis. This study provides a mechanism for DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families.

Identifiants

pubmed: 39174524
doi: 10.1038/s41467-024-51310-z
pii: 10.1038/s41467-024-51310-z
doi:

Substances chimiques

Membrane Proteins 0
Guanine Nucleotide Exchange Factors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7239

Subventions

Organisme : Deutscher Akademischer Austauschdienst (German Academic Exchange Service)
ID : 57166498
Organisme : Ontario Genomics Institute (OGI)
ID : OGI-147
Organisme : Ontario Genomics Institute (OGI)
ID : OGI-147
Organisme : Ontario Genomics Institute (OGI)
ID : OGI-147
Organisme : U.S. Department of Health & Human Services | NIH | Office of Strategic Coordination (OSC)
ID : U01HG007943
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : NS105078
Organisme : U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)
ID : HG011758

Investigateurs

Heidi Cope (H)

Informations de copyright

© 2024. The Author(s).

Références

Raga, S., Specchio, N., Rheims, S. & Wilmshurst, J. M. Developmental and epileptic encephalopathies: recognition and approaches to care. Epileptic Disord. 23, 40–52 (2021).
pubmed: 33632673 doi: 10.1684/epd.2021.1244
Han, C. et al. Epileptic encephalopathy caused by mutations in the guanine nucleotide exchange factor DENND5A. Am. J. Hum. Genet. 99, 1359–1367 (2016).
pubmed: 27866705 pmcid: 5142110 doi: 10.1016/j.ajhg.2016.10.006
Anazi, S. et al. Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield. Mol. Psychiatry 22, 615–624 (2017).
pubmed: 27431290 doi: 10.1038/mp.2016.113
Marat, A. L., Dokainish, H. & McPherson, P. S. DENN domain proteins: regulators of Rab GTPases. J. Biol. Chem. 286, 13791–13800 (2011).
pubmed: 21330364 pmcid: 3077579 doi: 10.1074/jbc.R110.217067
Callebaut, I., de Gunzburg, J., Goud, B. & Mornon, J. P. RUN domains: a new family of domains involved in Ras-like GTPase signaling. Trends Biochem. Sci. 26, 79–83 (2001).
pubmed: 11166556 doi: 10.1016/S0968-0004(00)01730-8
Janoueix-Lerosey, I., Jollivet, F., Camonis, J., Marche, P. N. & Goud, B. Two-hybrid system screen with the small GTP-binding protein Rab6. Identification of a novel mouse GDP dissociation inhibitor isoform and two other potential partners of Rab6. J. Biol. Chem. 270, 14801–14808 (1995).
pubmed: 7782346 doi: 10.1074/jbc.270.24.14801
Recacha, R. et al. Structural basis for recruitment of Rab6-interacting protein 1 to Golgi via a RUN domain. Structure 17, 21–30 (2009).
pubmed: 19141279 doi: 10.1016/j.str.2008.10.014
Fernandes, H., Franklin, E. & Khan, A. R. Crystallization of an engineered RUN domain of Rab6-interacting protein 1/DENND5. Acta Crystallogr. Sect. F. Struct. Biol. Cryst. Commun. 67, 556–560 (2011).
pubmed: 21543860 pmcid: 3087639 doi: 10.1107/S174430911100724X
Fernandes, H., Franklin, E., Jollivet, F., Bliedtner, K. & Khan, A. R. Mapping the interactions between a RUN domain from DENND5/Rab6IP1 and sorting nexin 1. PLoS One 7, e35637 (2012).
pubmed: 22558185 pmcid: 3338420 doi: 10.1371/journal.pone.0035637
Wassmer, T. et al. The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network. Dev. Cell 17, 110–122 (2009).
pubmed: 19619496 pmcid: 2714578 doi: 10.1016/j.devcel.2009.04.016
Miserey-Lenkei, S. et al. Rab6-interacting protein 1 links Rab6 and Rab11 function. Traffic 8, 1385–1403 (2007).
pubmed: 17725553 doi: 10.1111/j.1600-0854.2007.00612.x
Li, Y. et al. Cancer driver candidate genes AVL9, DENND5A and NUPL1 contribute to MDCK cystogenesis. Oncoscience 1, 854–865 (2014).
pubmed: 25621300 pmcid: 4303893 doi: 10.18632/oncoscience.107
Yang, M. et al. Novel loss-of-function variant in DENND5A impedes melanosomal cargo transport and predisposes to familial cutaneous melanoma. Genet. Med. 24, 157–169 (2022).
pubmed: 34906508 doi: 10.1016/j.gim.2021.09.003
Navis A., Bagnat, M. Apicobasal Polarity and Lumen Formation During Development (Springer, 2015).
Lamus, F. et al. FGF2/EGF contributes to brain neuroepithelial precursor proliferation and neurogenesis in rat embryos: the involvement of embryonic cerebrospinal fluid. Dev. Dyn. 249, 141–153 (2020).
pubmed: 31736174 doi: 10.1002/dvdy.135
Fame, R. M., Cortes-Campos, C. & Sive, H. L. Brain ventricular system and cerebrospinal fluid development and function: light at the end of the tube: a primer with latest insights. Bioessays 42, e1900186 (2020). 2020.
pubmed: 32078177 doi: 10.1002/bies.201900186
O’Driscoll, M. C. et al. Recessive mutations in the gene encoding the tight junction protein occludin cause band-like calcification with simplified gyration and polymicrogyria. Am. J. Hum. Genet. 87, 354–364 (2010).
pubmed: 20727516 pmcid: 2933344 doi: 10.1016/j.ajhg.2010.07.012
Al-Dosari, M. S. et al. Mutation in MPDZ causes severe congenital hydrocephalus. J. Med. Genet. 50, 54–58 (2013).
pubmed: 23240096 doi: 10.1136/jmedgenet-2012-101294
Sterling, N. et al. De novo variants in MPP5 cause global developmental delay and behavioral changes. Hum. Mol. Genet. 29, 3388–3401 (2020).
pubmed: 33073849 pmcid: 7906781 doi: 10.1093/hmg/ddaa224
Zanotta N., et al. A case of a childhood onset developmental encephalopathy with a novel de novo truncating variant in the Membrane Protein Palmitoylated 5 (MPP5) gene. Seizure. https://doi.org/10.1016/j.seizure.2023.01.015 (2023).
Bendriem R. M., Singh S., Aleem A. A., Antonetti D. A., Ross M. E. Tight junction protein occludin regulates progenitor self-renewal and survival in developing cortex. Elife. 8. https://doi.org/10.7554/eLife.49376 (2019).
Abdel-Hamid, M. S., Abdel-Salam, G. M. H., Issa, M. Y., Emam, B. A. & Zaki, M. S. Band-like calcification with simplified gyration and polymicrogyria: report of 10 new families and identification of five novel OCLN mutations. J. Hum. Genet. 62, 553–559 (2017).
pubmed: 28179633 doi: 10.1038/jhg.2017.4
Kim, S. et al. The apical complex couples cell fate and cell survival to cerebral cortical development. Neuron 66, 69–84 (2010).
pubmed: 20399730 pmcid: 2872122 doi: 10.1016/j.neuron.2010.03.019
Yamaguchi, M., Imai, F., Tonou-Fujimori, N. & Masai, I. Mutations in N-cadherin and a Stardust homolog, Nagie oko, affect cell-cycle exit in zebrafish retina. Mech. Dev. 127, 247–264 (2010).
pubmed: 20362667 doi: 10.1016/j.mod.2010.03.004
Assemat, E., Bazellieres, E., Pallesi-Pocachard, E., Le Bivic, A. & Massey-Harroche, D. Polarity complex proteins. Biochim. Biophys. Acta 1778, 614–630 (2008).
pubmed: 18005931 doi: 10.1016/j.bbamem.2007.08.029
Tepass, U., Theres, C. & Knust, E. crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell 61, 787–799 (1990).
pubmed: 2344615 doi: 10.1016/0092-8674(90)90189-L
Adachi, M. et al. Similar and distinct properties of MUPP1 and Patj, two homologous PDZ domain-containing tight-junction proteins. Mol. Cell Biol. 29, 2372–2389 (2009).
pubmed: 19255144 pmcid: 2668367 doi: 10.1128/MCB.01505-08
Saugier-Veber, P. et al. Hydrocephalus due to multiple ependymal malformations is caused by mutations in the MPDZ gene. Acta Neuropathol. Commun. 5, 36 (2017).
pubmed: 28460636 pmcid: 5412059 doi: 10.1186/s40478-017-0438-4
Feldner, A. et al. Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice. EMBO Mol. Med. 9, 890–905 (2017).
pubmed: 28500065 pmcid: 5494508 doi: 10.15252/emmm.201606430
Yang J., et al. Murine MPDZ-linked hydrocephalus is caused by hyperpermeability of the choroid plexus. EMBO Mol. Med.11 https://doi.org/10.15252/emmm.201809540 (2019).
Serra, R. & Simard, J. M. Adherens, tight, and gap junctions in ependymal cells: a systematic review of their contribution to CSF-brain barrier. Front. Neurol. 14, 1092205 (2023).
pubmed: 37034077 pmcid: 10079940 doi: 10.3389/fneur.2023.1092205
Shah, P. T. et al. Single-cell transcriptomics and fate mapping of ependymal cells reveals an absence of neural stem cell function. Cell 173, 1045–1057.e9 (2018).
pubmed: 29727663 doi: 10.1016/j.cell.2018.03.063
Eze, U. C., Bhaduri, A., Haeussler, M., Nowakowski, T. J. & Kriegstein, A. R. Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia. Nat. Neurosci. 24, 584–594 (2021).
pubmed: 33723434 pmcid: 8012207 doi: 10.1038/s41593-020-00794-1
Boroviak, T. & Rashbass, P. The apical polarity determinant Crumbs 2 is a novel regulator of ESC-derived neural progenitors. Stem Cells 29, 193–205 (2011).
pubmed: 21732478 doi: 10.1002/stem.567
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
pubmed: 34265844 pmcid: 8371605 doi: 10.1038/s41586-021-03819-2
Varadi, M. et al. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 50, D439–D444 (2022).
pubmed: 34791371 doi: 10.1093/nar/gkab1061
Wu, X. et al. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. Proc. Natl Acad. Sci. USA 108, 18672–18677 (2011).
pubmed: 22065758 pmcid: 3219131 doi: 10.1073/pnas.1110415108
Liu, X., Bolteus, A. J., Balkin, D. M., Henschel, O. & Bordey, A. GFAP-expressing cells in the postnatal subventricular zone display a unique glial phenotype intermediate between radial glia and astrocytes. Glia 54, 394–410 (2006).
pubmed: 16886203 doi: 10.1002/glia.20392
Garcia, A. D., Doan, N. B., Imura, T., Bush, T. G. & Sofroniew, M. V. GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat. Neurosci. 7, 1233–1241 (2004).
pubmed: 15494728 doi: 10.1038/nn1340
Zhang, X. Z. et al. Folic acid rescues valproic acid-induced morphogenesis inhibition in neural rosettes derived from human pluripotent stem cells. Front. Cell Neurosci. 16, 888152 (2022).
pubmed: 35651759 pmcid: 9148965 doi: 10.3389/fncel.2022.888152
Fedorova, V. et al. Differentiation of neural rosettes from human pluripotent stem cells in vitro is sequentially regulated on a molecular level and accomplished by the mechanism reminiscent of secondary neurulation. Stem Cell Res. 40, 101563 (2019).
pubmed: 31494448 doi: 10.1016/j.scr.2019.101563
Townshend, R. F. et al. Effect of cell spreading on rosette formation by human pluripotent stem cell-derived neural progenitor cells. Front. Cell Dev. Biol. 8, 588941 (2020).
pubmed: 33178701 pmcid: 7593581 doi: 10.3389/fcell.2020.588941
Grill, S. W. & Hyman, A. A. Spindle positioning by cortical pulling forces. Dev. Cell 8, 461–465 (2005).
pubmed: 15809029 doi: 10.1016/j.devcel.2005.03.014
Guemez-Gamboa, A. et al. Loss of protocadherin-12 leads to diencephalic-mesencephalic junction dysplasia syndrome. Ann. Neurol. 84, 638–647 (2018).
pubmed: 30178464 pmcid: 6510237 doi: 10.1002/ana.25327
Accogli, A. et al. PCDH12 variants are associated with basal ganglia anomalies and exudative vitreoretinopathy. Eur. J. Med. Genet. 65, 104405 (2022).
pubmed: 34929393 doi: 10.1016/j.ejmg.2021.104405
Fazeli, W. et al. The phenotypic spectrum of PCDH12 associated disorders—five new cases and review of the literature. Eur. J. Paediatr. Neurol. 36, 7–13 (2022).
pubmed: 34773825 doi: 10.1016/j.ejpn.2021.10.011
Romaniello, R. et al. Tubulin genes and malformations of cortical development. Eur. J. Med Genet 61, 744–754 (2018).
pubmed: 30016746 doi: 10.1016/j.ejmg.2018.07.012
Hung K. L., Lu J. F., Su D. J., Hsu S. J., Wang L. C. Tubulinopathy presenting as developmental and epileptic encephalopathy. Children 9. https://doi.org/10.3390/children9081105 (2022).
Brock, S. et al. Defining the phenotypical spectrum associated with variants in TUBB2A. J. Med. Genet. 58, 33–40 (2021).
pubmed: 32571897 doi: 10.1136/jmedgenet-2019-106740
Lee, Y. H. & Park, N. H. A complex cortical malformation caused by a mutation in the tubulin-encoding TUBB3 gene. Taehan Yongsang Uihakhoe Chi 81, 1246–1249 (2020).
pubmed: 36238036
Maillard, C. et al. Tubulin mutations in human neurodevelopmental disorders. Semin Cell Dev. Biol. 137, 87–95 (2023).
pubmed: 35915025 doi: 10.1016/j.semcdb.2022.07.009
Saillour, Y. et al. LIS1-related isolated lissencephaly: spectrum of mutations and relationships with malformation severity. Arch. Neurol. 66, 1007–1015 (2009).
pubmed: 19667223 doi: 10.1001/archneurol.2009.149
Teissier, N. et al. Cytomegalovirus-induced brain malformations in fetuses. J. Neuropathol. Exp. Neurol. 73, 143–158 (2014).
pubmed: 24423639 doi: 10.1097/NEN.0000000000000038
Vivarelli, R. et al. Pseudo-TORCH syndrome or Baraitser-Reardon syndrome: diagnostic criteria. Brain Dev. 23, 18–23 (2001).
pubmed: 11226724 doi: 10.1016/S0387-7604(00)00188-1
Tessier, A. et al. Bi-allelic variations in CRB2, encoding the crumbs cell polarity complex component 2, lead to non-communicating hydrocephalus due to atresia of the aqueduct of sylvius and central canal of the medulla. Acta Neuropathol. Commun. 11, 29 (2023).
pubmed: 36803301 pmcid: 9940441 doi: 10.1186/s40478-023-01519-8
Lamont, R. E. et al. Expansion of phenotype and genotypic data in CRB2-related syndrome. Eur. J. Hum. Genet. 24, 1436–1444 (2016).
pubmed: 27004616 pmcid: 5027675 doi: 10.1038/ejhg.2016.24
Slavotinek, A. et al. CRB2 mutations produce a phenotype resembling congenital nephrosis, Finnish type, with cerebral ventriculomegaly and raised alpha-fetoprotein. Am. J. Hum. Genet. 96, 162–169 (2015).
pubmed: 25557780 pmcid: 4289687 doi: 10.1016/j.ajhg.2014.11.013
Gloerich, M., Bianchini, J. M., Siemers, K. A., Cohen, D. J. & Nelson, W. J. Cell division orientation is coupled to cell-cell adhesion by the E-cadherin/LGN complex. Nat. Commun. 8, 13996 (2017).
pubmed: 28045117 pmcid: 5216124 doi: 10.1038/ncomms13996
Peyre, E. et al. A lateral belt of cortical LGN and NuMA guides mitotic spindle movements and planar division in neuroepithelial cells. J. Cell Biol. 193, 141–154 (2011).
pubmed: 21444683 pmcid: 3082188 doi: 10.1083/jcb.201101039
Zheng, Z. et al. LGN regulates mitotic spindle orientation during epithelial morphogenesis. J. Cell Biol. 189, 275–288 (2010).
pubmed: 20385777 pmcid: 2856901 doi: 10.1083/jcb.200910021
Konno, D. et al. Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nat. Cell Biol. 10, 93–101 (2008).
pubmed: 18084280 doi: 10.1038/ncb1673
Du, Q., Taylor, L., Compton, D. A. & Macara, I. G. LGN blocks the ability of NuMA to bind and stabilize microtubules. A mechanism for mitotic spindle assembly regulation. Curr. Biol. 12, 1928–1933 (2002).
pubmed: 12445386 doi: 10.1016/S0960-9822(02)01298-8
Woodruff, J. B., Drubin, D. G. & Barnes, G. Dynein-driven mitotic spindle positioning restricted to anaphase by She1p inhibition of dynactin recruitment. Mol. Biol. Cell 20, 3003–3011 (2009).
pubmed: 19403691 pmcid: 2704152 doi: 10.1091/mbc.e09-03-0186
Mora-Bermudez, F., Matsuzaki, F. & Huttner, W. B. Specific polar subpopulations of astral microtubules control spindle orientation and symmetric neural stem cell division. Elife 3, e02875 (2014).
Taverna, E. et al. Non-canonical features of the Golgi apparatus in bipolar epithelial neural stem cells. Sci. Rep. 6, 21206 (2016).
pubmed: 26879757 pmcid: 4754753 doi: 10.1038/srep21206
Taverna, E. & Huttner, W. B. The Golgi apparatus in polarized neuroepithelial stem cells and their progeny: canonical and noncanonical features. Results Probl. Cell Differ. 67, 359–375 (2019).
pubmed: 31435803 doi: 10.1007/978-3-030-23173-6_15
Jean, F., Stuart, A. & Tarailo-Graovac, M. Dissecting the genetic and etiological causes of primary microcephaly. Front. Neurol. 11, 570830 (2020).
pubmed: 33178111 pmcid: 7593518 doi: 10.3389/fneur.2020.570830
Knoblich, J. A. Mechanisms of asymmetric stem cell division. Cell 132, 583–597 (2008).
pubmed: 18295577 doi: 10.1016/j.cell.2008.02.007
Aaku-Saraste, E., Oback, B., Hellwig, A. & Huttner, W. B. Neuroepithelial cells downregulate their plasma membrane polarity prior to neural tube closure and neurogenesis. Mech. Dev. 69, 71–81 (1997).
pubmed: 9486532 doi: 10.1016/S0925-4773(97)00156-1
Aaku-Saraste, E., Hellwig, A. & Huttner, W. B. Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure–remodeling of the neuroepithelium prior to neurogenesis. Dev. Biol. 180, 664–679 (1996).
pubmed: 8954735 doi: 10.1006/dbio.1996.0336
Sobreira, N., Schiettecatte, F., Valle, D. & Hamosh, A. GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum. Mutat. 36, 928–930 (2015).
pubmed: 26220891 pmcid: 4833888 doi: 10.1002/humu.22844
Landrum, M. J. et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 46, D1062–D1067 (2018).
pubmed: 29165669 doi: 10.1093/nar/gkx1153
McLaren, W. et al. Deriving the consequences of genomic variants with the Ensembl API and SNP effect predictor. Bioinformatics 26, 2069–2070 (2010).
pubmed: 20562413 pmcid: 2916720 doi: 10.1093/bioinformatics/btq330
Chirita-Emandi, A., Doros, G., Simina, I. J., Gafencu, M. & Puiu, M. Head circumference references for school age children in western Romania. Rev. Med. Chir. Soc. Med Nat. Iasi 119, 1083–1091 (2015).
pubmed: 26793853
Chen C. X. et al. A multistep workflow to evaluate newly generated ipscs and their ability to generate different cell types. Methods Protoc. 4. https://doi.org/10.3390/mps4030050 (2021).
Okita, K. et al. A more efficient method to generate integration-free human iPS cells. Nat. Methods 8, 409–412 (2011).
pubmed: 21460823 doi: 10.1038/nmeth.1591
Hauser, S. et al. Establishment of SPAST mutant induced pluripotent stem cells (iPSCs) from a hereditary spastic paraplegia (HSP) patient. Stem Cell Res. 17, 485–488 (2016).
pubmed: 27789400 doi: 10.1016/j.scr.2016.09.022
Johannessen, C. M. et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468, 968–972 (2010).
Chilov, D. et al. Phosphorylated beta-catenin localizes to centrosomes of neuronal progenitors and is required for cell polarity and neurogenesis in developing midbrain. Dev. Biol. 357, 259–268 (2011).
pubmed: 21736876 doi: 10.1016/j.ydbio.2011.06.029
LaFave, M. C., Varshney, G. K., Vemulapalli, M., Mullikin, J. C. & Burgess, S. M. A defined zebrafish line for high-throughput genetics and genomics: NHGRI-1. Genetics 198, 167–170 (2014).
pubmed: 25009150 pmcid: 4174928 doi: 10.1534/genetics.114.166769
Varshney, G. K. et al. A high-throughput functional genomics workflow based on CRISPR/Cas9-mediated targeted mutagenesis in zebrafish. Nat. Protoc. 11, 2357–2375 (2016).
pubmed: 27809318 pmcid: 5630457 doi: 10.1038/nprot.2016.141
Lin, S. J. et al. Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish. Genet Med. 23, 1933–1943 (2021).
pubmed: 34172899 pmcid: 8956360 doi: 10.1038/s41436-021-01239-1
Lin, S. J. et al. Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function. Hum. Mutat. 43, 1472–1489 (2022).
pubmed: 35815345 doi: 10.1002/humu.24435
Thisse, B. & Thisse, C. In situ hybridization on whole-mount zebrafish embryos and young larvae. Methods Mol. Biol. 1211, 53–67 (2014).
Yushkevich, P. A. et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage 31, 1116–1128 (2006).
pubmed: 16545965 doi: 10.1016/j.neuroimage.2006.01.015
Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543–D552 (2022).
pubmed: 34723319 doi: 10.1093/nar/gkab1038

Auteurs

Emily Banks (E)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Vincent Francis (V)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Sheng-Jia Lin (SJ)

Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Fares Kharfallah (F)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Vladimir Fonov (V)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Maxime Lévesque (M)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Chanshuai Han (C)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Gopinath Kulasekaran (G)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Marius Tuznik (M)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Armin Bayati (A)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Reem Al-Khater (R)

Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.

Fowzan S Alkuraya (FS)

Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Loukas Argyriou (L)

Institute of Human Genetics, University Medical Center, Göttingen, Germany.

Meisam Babaei (M)

Department of Pediatrics, North Khorasan University of Medical Sciences, Bojnurd, Iran.

Melanie Bahlo (M)

Walter and Eliza Hall Institute for Medical Research, Parkville, VIC, Australia.

Behnoosh Bakhshoodeh (B)

Mashhad University of Medical Sciences, Mashhad, Iran.

Eileen Barr (E)

Department of Human Genetics, Emory University, Atlanta, GA, USA.

Lauren Bartik (L)

University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USA.
Department of Pediatrics, Division of Clinical Genetics, Children's Mercy Hospital, Kansas City, MO, USA.

Mahmoud Bassiony (M)

Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Miriam Bertrand (M)

Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.

Dominique Braun (D)

Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Rebecca Buchert (R)

Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.

Mauro Budetta (M)

Paediatric and Child Neurology Unit, Cava de' Tirreni AOU S. Giovanni di Dio e Ruggiero d'Aragona Hospital, Salerno, Italy.

Maxime Cadieux-Dion (M)

Department of Pathology and Laboratory Medicine, Children's Mercy Hospital, Kansas City, MO, USA.

Daniel G Calame (DG)

Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Texas Children's Hospital, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Heidi Cope (H)

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

Donna Cushing (D)

Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, ON, Canada.

Stephanie Efthymiou (S)

Department of Neuromuscular Diseases, University College London (UCL) Queen Square Institute of Neurology, London, UK.

Marwa Abd Elmaksoud (MA)

Neurology Unit, Department of Pediatrics, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.

Huda G El Said (HG)

Neurology Unit, Department of Pediatrics, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.

Tawfiq Froukh (T)

Department of Biotechnology and Genetic Engineering, Philadelphia University, Amman, Jordan.

Harinder K Gill (HK)

Provincial Medical Genetics Program at BC Women's Health Centre, Vancouver, BC, Canada.

Joseph G Gleeson (JG)

Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Rady Children's Institute for Genomic Medicine, San Diego, CA, USA.

Laura Gogoll (L)

Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Elaine S-Y Goh (ES)

Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, ON, Canada.

Vykuntaraju K Gowda (VK)

Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.

Tobias B Haack (TB)

Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.

Mais O Hashem (MO)

Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Stefan Hauser (S)

German Center of Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Center for Neurology and Hertie Institute for Clinical Brain Research, University Tübingen, Tübingen, 72076, Germany.

Trevor L Hoffman (TL)

Department of Regional Genetics, Southern California Kaiser Permanente Medical Group, Anaheim, CA, USA.

Jacob S Hogue (JS)

Madigan Army Medical Center, Tacoma, WA, USA.

Akimoto Hosokawa (A)

Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.

Henry Houlden (H)

Department of Neuromuscular Diseases, University College London (UCL) Queen Square Institute of Neurology, London, UK.

Kevin Huang (K)

Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Stephanie Huynh (S)

Provincial Medical Genetics Program at BC Women's Health Centre, Vancouver, BC, Canada.

Ehsan G Karimiani (EG)

Molecular and Clinical Sciences Institute, St. George's, University of London, Cranmer Terrace, London, UK.
Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran.

Silke Kaulfuß (S)

Institute of Human Genetics, University Medical Center, Göttingen, Germany.

G Christoph Korenke (GC)

Department of Neuropediatrics, University Children's Hospital, Klinikum Oldenburg, Oldenburg, Germany.

Amy Kritzer (A)

Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.

Hane Lee (H)

3billion Inc, Seoul, South Korea.

James R Lupski (JR)

Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Texas Children's Hospital, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.

Elysa J Marco (EJ)

Cortica Healthcare, San Rafael, CA, USA.

Kirsty McWalter (K)

GeneDx, Gaithersburg, MD, USA.

Arakel Minassian (A)

Centre for Applied Genomics, Genetics, and Genome Biology, Hospital for Sick Children, Toronto, ON, Canada.

Berge A Minassian (BA)

Department of Pediatrics and Neurology, UT Southwestern Medical Center, Dallas, TX, USA.

David Murphy (D)

Department of Clinical and Movement Neurosciences, University College London (UCL) Queen Square Institute of Neurology, London, UK.

Juanita Neira-Fresneda (J)

Department of Human Genetics, Emory University, Atlanta, GA, USA.

Hope Northrup (H)

Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) and Children's Memorial Hermann Hospital, Houston, TX, USA.

Denis M Nyaga (DM)

Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.

Barbara Oehl-Jaschkowitz (B)

BIOSCIENTIA-MVZ-Labor-Saar-Practice of Human Genetics, Homburg (Saar), Germany.

Matthew Osmond (M)

Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.

Richard Person (R)

GeneDx, Gaithersburg, MD, USA.

Davut Pehlivan (D)

Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Texas Children's Hospital, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Cassidy Petree (C)

Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Lynette G Sadleir (LG)

Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.

Carol Saunders (C)

University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USA.
Department of Pathology and Laboratory Medicine, Children's Mercy Hospital, Kansas City, MO, USA.
Center for Pediatric Genomic Medicine Children's Mercy, Kansas City, MO, USA.

Ludger Schoels (L)

German Center of Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Center for Neurology and Hertie Institute for Clinical Brain Research, University Tübingen, Tübingen, 72076, Germany.

Vandana Shashi (V)

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

Rebecca C Spillmann (RC)

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

Varunvenkat M Srinivasan (VM)

Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.

Paria N Torbati (PN)

Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran.

Tulay Tos (T)

Department of Medical Genetics, University of Health Sciences, Zubeyde Hanim Research and Training Hospital of Women's Health and Diseases, Ankara, Turkey.

Maha S Zaki (MS)

Human Genetics and Genome Research Institute, Clinical Genetics Department, National Research Centre, Cairo, Egypt.

Dihong Zhou (D)

University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USA.
Department of Pediatrics, Division of Clinical Genetics, Children's Mercy Hospital, Kansas City, MO, USA.

Christiane Zweier (C)

Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Jean-François Trempe (JF)

Department of Pharmacology & Therapeutics and Centre de Recherche en Biologie Structurale, McGill University, Montréal, QC, Canada.

Thomas M Durcan (TM)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Ziv Gan-Or (Z)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.
Department of Human Genetics, McGill University, Montréal, QC, Canada.

Massimo Avoli (M)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.

Cesar Alves (C)

Division of Neuroradiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Gaurav K Varshney (GK)

Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Reza Maroofian (R)

Department of Neuromuscular Diseases, University College London (UCL) Queen Square Institute of Neurology, London, UK.

David A Rudko (DA)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada.
McConnell Brain Imaging Centre, the Neuro, Montréal, QC, Canada.
Department of Biomedical Engineering, McGill University, Montréal, QC, Canada.

Peter S McPherson (PS)

Department of Neurology and Neurosurgery, the Neuro, McGill University, Montréal, QC, Canada. peter.mcpherson@mcgill.ca.

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