Pathological Mechanisms of Human Cerebeller Malformations
Pathological Mechanisms of Human Cerebeller Malformations
批准号:
10076489
负责人:
Kathleen Joyce Millen
金额:
$9.97万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-02-15 至 2021-06-30
关键词:
6p25AffectBehaviorBiological ModelsBrainBrain DiseasesCandidate Disease GeneCell Culture TechniquesCell Differentiation processCellsCellular AssayCerebellar DiseasesCerebellar malformationCerebellar vermis structureCognitiveCongenital AbnormalityCytoplasmic GranulesDandy-Walker SyndromeDataData SetDatabasesDefectDevelopmentDiagnosisDiseaseEmbryoEnsureEtiologyEventExpression ProfilingFOXC1 geneFoundationsGene ExpressionGenesGenetic TranscriptionGolgi ApparatusHigh-Throughput Nucleotide SequencingHistologicHistologyHumanHuman PathologyImageImmunohistochemistryIn SituIntellectual functioning disabilityJoubert syndromeKnowledgeLeadLip structureLive BirthManuscriptsModelingMolecularMolecular AnalysisMolecular ProfilingMorphologyMotorMusMutationNeuronal DifferentiationNeuronsPathogenesisPathologicPathologyPathway interactionsPatientsPopulationPregnancyPublishingPurkinje CellsResourcesSignal TransductionSliceStainsTestingTissue SampleTranscriptVentricularactivation-induced cytidine deaminaseautism spectrum disordercell behaviorcell typecohortcommon treatmentcresyl violetexomeexperimental studyfetalfetal diagnosisgene discoverygenetic analysisgranule cellhistogenesishuman RNA sequencinghuman datahuman fetal cellshuman fetal cerebellar tissuehuman fetal samplehuman fetus tissuehuman pluripotent stem cellimprovedin uteroinsightknowledge baselaser capture microdissectionmalformationmotor deficitmouse modelneurogenesisneuroimagingphysically handicappedpostnatalprenatalsensory integrationtranscriptome
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
Numerous cerebellar malformations have been described in humans. Most cause cognitive, in addition to
motor and sensory integration deficits. Surprisingly little is understood regarding the developmental basis of
these malformations, particularly since little human specific data is available for normal or abnormal fetal
cerebellar development. This proposal seeks to advance knowledge of human cerebellar development and
malformations using human fetal samples and mouse models. The human-specific data will directly test the
validity of our working mouse-derived hypotheses regarding the causes these disorders and strengthen the
foundation of normal developmental data which will inform our ongoing genetic analyses of human cerebellar
malformations. We will conduct the first in-depth analysis of normal human fetal cerebellar development from
4-23 Gestational Weeks, covering major developmental events. We will then examine the pathology of human
fetal Dandy-Walker malformation the most common human cerebellar malformation, affecting ~1/3000 live
births. Mouse models will be generated in conjunction with these experiments to assess the mechanisms of the
developmental pathology. Finally, we will generate the first transcriptome data for normal human fetal
cerebellar neurons. These cell-type specific data are critically missing from current publicly available brain
resources. Our human fetal cerebellar neuron data will be compared to transcriptome data from existing
datasets of endogenous mouse developing cerebellar neurons as well as mES and hPSC-derived cerebellar
neurons to development to assess their validity as model systems. Further, the data will also be integrated with
exome data from human cerebellar malformation patients to facilitate gene discovery for these important and
understudied birth defects.
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DOI:
10.1016/b978-0-444-63956-1.00002-3
发表时间:
2018-01-01
期刊:
Handbook of clinical neurology
影响因子:
--
作者:
[Haldipur, Parthiv, Dang, Derek, Millen, Kathleen J]
通讯作者:
Millen, Kathleen J
DOI:
10.1016/j.neulet.2018.05.032
发表时间:
2019-01-01
期刊:
Neuroscience letters
影响因子:
2.5
作者:
[Haldipur P, Millen KJ]
通讯作者:
Millen KJ
DOI:
10.1007/s00401-021-02355-7
发表时间:
2021-10
期刊:
Acta neuropathologica
影响因子:
12.7
作者:
[Haldipur P, Bernardo S, Aldinger KA, Sivakumar T, Millman J, Sjoboen AH, Dang D, Dubocanin D, Deng M, Timms AE, Davis BD, Plummer JT, Mankad K, Oztekin O, Manganaro L, Guimiot F, Adle-Biassette H, Russo R, Siebert JR, Kidron D, Petrilli G, Roux N, Razavi F, Glass IA, Di Gioia C, Silvestri E, Millen KJ]
通讯作者:
Millen KJ
Human KCNQ5 de novo mutations underlie epilepsy and intellectual disability.
人类 KCNQ5 从头突变是癫痫和智力障碍的基础。
DOI:
10.1152/jn.00509.2021
发表时间:
2022
期刊:
Journal of neurophysiology
影响因子:
2.5
作者:
[Wei,AguanD, Wakenight,Paul, Zwingman,TheresaA, Bard,AngelaM, Sahai,Nikhil, Willemsen,MarjoleinH, Schelhaas,HeleniusJ, Stegmann,AlexanderPA, Verhoeven,JudithS, deMan,StellaA, Wessels,MarjaW, Kleefstra,Tjitske, Shinde,DeepaliN, Helb]
通讯作者:
Helb
Phenotypic outcomes in Mouse and Human Foxc1 dependent Dandy-Walker cerebellar malformation suggest shared mechanisms.
小鼠和人类FOXC1依赖的dandy-walker小脑畸形中的表型结局提出了共同的机制。
DOI:
10.7554/elife.20898
发表时间:
2017-01-16
期刊:
eLife
影响因子:
7.7
作者:
[Haldipur P, Dang D, Aldinger KA, Janson OK, Guimiot F, Adle-Biasette H, Dobyns WB, Siebert JR, Russo R, Millen KJ]
通讯作者:
Millen KJ
共 7 条
Building transgenic tools in Acomys cahirinus, an emerging model for mammalian regenerative biology and healthy aging
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批准号:10327728
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项目类别:
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资助金额:$23.56万
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财政年份:2021
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Mouse models of Pik3ca brain overgrowth disorders
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批准号:9331300
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资助金额:$55.91万
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财政年份:2017
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依托单位:
Mouse models of Pik3ca brain overgrowth disorders
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批准号:9905565
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项目类别:
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资助金额:$60.5万
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财政年份:2017
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New transgenic tools for mammalian fibrosis and regenerative repair research
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批准号:9331056
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资助金额:$27.49万
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财政年份:2017
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负责人:Kathleen Joyce Millen
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依托单位:
Pathological Mechanisms of Human Cerebellar Malformations
-
批准号:10456683
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项目类别:
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资助金额:$81.33万
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财政年份:2016
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负责人:Kathleen Joyce Millen
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依托单位:
Pathological Mechanisms of Human Cerebellar Malformations
-
批准号:10467630
-
项目类别:
-
资助金额:$35.36万
-
财政年份:2016
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负责人:Kathleen Joyce Millen
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依托单位:
Pathological Mechanisms of Human Cerebellar Malformations
-
批准号:10672203
-
项目类别:
-
资助金额:$78.79万
-
财政年份:2016
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负责人:Kathleen Joyce Millen
-
依托单位:
Megalencephaly and segmental brain overgrowth in humans
-
批准号:9751409
-
项目类别:
-
资助金额:$66.62万
-
财政年份:2015
-
负责人:Kathleen Joyce Millen
-
依托单位:
Congenital brain malformations caused by aberrant head mesenchymal signaling
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批准号:8539859
-
项目类别:
-
资助金额:$44.24万
-
财政年份:2012
-
负责人:Kathleen Joyce Millen
-
依托单位:
Congenital brain malformations caused by aberrant head mesenchymal signaling
-
批准号:9086446
-
项目类别:
-
资助金额:$51.11万
-
财政年份:2012
-
负责人:Kathleen Joyce Millen
-
依托单位:
Congenital brain malformations caused by aberrant head mesenchymal signaling
-
批准号:8852719
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项目类别:
-
资助金额:$44.24万
-
财政年份:2012
-
负责人:Kathleen Joyce Millen
-
依托单位:
Congenital brain malformations caused by aberrant head mesenchymal signaling
-
批准号:8667344
-
项目类别:
-
资助金额:$43.8万
-
财政年份:2012
-
负责人:Kathleen Joyce Millen
-
依托单位:
Congenital brain malformations caused by aberrant head mesenchymal signaling
-
批准号:8458757
-
项目类别:
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资助金额:$45.85万
-
财政年份:2012
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负责人:Kathleen Joyce Millen
-
依托单位:
Dorsal midline patterning in the vertebrate CNS
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批准号:8535228
-
项目类别:
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资助金额:$46.1万
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财政年份:2010
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负责人:Kathleen Joyce Millen
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依托单位:
Dorsal midline patterning in the vertebrate CNS
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批准号:8706991
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项目类别:
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资助金额:$47.3万
-
财政年份:2010
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负责人:Kathleen Joyce Millen
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依托单位:
Dorsal midline patterning in the vertebrate CNS
-
批准号:8152244
-
项目类别:
-
资助金额:$46.68万
-
财政年份:2010
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负责人:Kathleen Joyce Millen
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依托单位:
Dorsal midline patterning in the vertebrate CNS
-
批准号:8311069
-
项目类别:
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资助金额:$47.78万
-
财政年份:2010
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负责人:Kathleen Joyce Millen
-
依托单位:
Dorsal midline patterning in the vertebrate CNS
-
批准号:8025400
-
项目类别:
-
资助金额:$41.7万
-
财政年份:2010
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负责人:Kathleen Joyce Millen
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依托单位:
Rapid and inexpensive screening of disease candidate genes in mice
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批准号:7824652
-
项目类别:
-
资助金额:$50.0万
-
财政年份:2009
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负责人:Kathleen Joyce Millen
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依托单位:
Rapid and inexpensive screening of disease candidate genes in mice
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批准号:7942828
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项目类别:
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资助金额:$50.0万
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财政年份:2009
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负责人:Kathleen Joyce Millen
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依托单位:
海外基金