Investigation of Mammalian Retinal Neuron Development

哺乳动物视网膜神经元发育的研究

基本信息

批准号：
9902448
负责人：
Nadean L Brown
金额：
$ 45.66万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902448
关键词：
ATOH7 gene Address Adopted Adult Affect Alagille Syndrome Animal Model Anophthalmos Apoptosis Biochemical Bioinformatics Biological Assay Brain Cell Differentiation process Cell Maintenance Cell Proliferation Cells Childhood Chimeric Proteins Coloboma Complex Confocal Microscopy Data Deformity Development Disease EMSA Embryo Embryology Embryonic Development Exhibits Eye Eye Development Fissural Flow Cytometry Gene Targeting Genes Genetic Epistasis Glaucoma Goals Grant Histology Human Immunohistochemistry In Situ Hybridization Inherited Investigation Knowledge Leber&apos s amaurosis Liver Malignant Neoplasms Methods Microphthalmos Molecular Morphogenesis Mouse Strains Mus Mutant Strains Mice Mutation Neurons Notch Signaling Pathway Optic Disk Optic Nerve Optic Neuritis Optics Osteogenesis Pathogenesis Pathogenicity Pathway interactions Patients Phenocopy Phenotype Photoreceptors Primary Open Angle Glaucoma Process Publishing Regulation Research Research Project Grants Resources Retina Retinal Cone Retinal Diseases Retinal Ganglion Cells Role Signal Transduction Site Technology Testing Transcription Repressor Transgenic Organisms Work cardiogenesis conditional mutant developmental genetics experimental study eye formation genetic risk factor genetic testing genome wide association study human disease in vivo mouse model mutant neurogenesis neuron development next generation sequencing notch protein optic nerve disorder optic stalk prenatal public health relevance response retinal neuron retinal progenitor cell stem cells transcription factor transcriptome transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): This proposal investigates the underlying causes of human ocular diseases using mouse models, focusing on both the Notch signaling pathway, which is broadly required during development, and two classes of bHLH transcription factors (Atoh7/Neurog2 or Hes genes). The activities of both types of factors are regulated by Notch signaling, in particular developmental contexts. The Notch pathway is also responsible for regulating cell proliferation, morphogenesis, differentiation, apoptosis and stem cell maintenance. Dominant mutations in the human Notch pathway genes JAG1 and NOTCH2 cause Alagille syndrome, in which some patients exhibit eye deformities. This proposal will use complex conditional (cre-lox) mouse strains, including double and triple mutants, histology, immunohistochemistry, confocal microscopy, in situ hybridization, mouse embryology, flow cytometry, NEXTgen sequencing, bioinformatics, ChIP, qPCR, and PCR technologies to address basic, mechanistic questions about retinal neuron formation. We will address two important questions, namely 1) Which genes regulate optic nerve head development and maintain the boundary between the retina and optic stalk? 2) What controls retinal progenitor cell differentiation into either a retinal ganglion cell or a cone photoreceptor neuron?

描述（由申请人提供）：本提案利用小鼠模型研究人类眼部疾病的根本原因，重点关注发育过程中广泛需要的Notch信号通路和两类bHLH转录因子（Atoh7/Neurog2或Hes基因）两种类型因子的活性均受 Notch 信号传导调节，特别是在发育过程中，Notch 信号通路还负责调节细胞增殖、形态发生、分化、凋亡和干细胞维持。人类Notch通路基因JAG1和NOTCH2导致Alagille综合征，其中一些患者表现出眼睛畸形。该提案将使用复杂的条件（cre-lox）小鼠品系，包括双突变体和三突变体，进行组织学、免疫组织化学、共聚焦显微镜检查。杂交、小鼠胚胎学、流式细胞术、NEXTgen 测序、生物信息学、ChIP、qPCR 和 PCR 技术，以解决有关的基本机械问题我们将解决两个重要问题，即 1）哪些基因调节视神经乳头发育并维持视网膜和视柄之间的边界？ 2）什么控制视网膜祖细胞分化为视网膜神经节细胞或视锥细胞。神经元？

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Notch directs telencephalic development and controls neocortical neuron fate determination by regulating microRNA levels.

DOI：
10.1242/dev.201408
发表时间：
2023-06-01
期刊：
DEVELOPMENT
影响因子：
4.6
作者：
Han, Jisoo S;Fishman-Williams, Elizabeth;Decker, Steven C;Hino, Keiko;Reyes, Raenier V;Brown, Nadean L;Simo, Sergi;Torre, Anna La
通讯作者：
Torre, Anna La

Neurog2 controls the leading edge of neurogenesis in the mammalian retina.

DOI：
10.1016/j.ydbio.2010.02.002
发表时间：
2010-04-15
期刊：
Developmental biology
影响因子：
2.7
作者：
Hufnagel RB;Le TT;Riesenberg AL;Brown NL
通讯作者：
Brown NL

Cell autonomous and nonautonomous requirements for Delltalike1 during early mouse retinal neurogenesis.

早期小鼠视网膜神经发生过程中 Delltalike1 的细胞自主和非自主需求。

DOI：
10.1002/dvdy.24402
发表时间：
2016
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
0
作者：
Riesenberg,AmyN;Brown,NadeanL
通讯作者：
Brown,NadeanL

Genome-wide association identifies ATOH7 as a major gene determining human optic disc size.

DOI：
10.1093/hmg/ddq144
发表时间：
2010-07-01
期刊：
Human molecular genetics
影响因子：
3.5
作者：
Macgregor S;Hewitt AW;Hysi PG;Ruddle JB;Medland SE;Henders AK;Gordon SD;Andrew T;McEvoy B;Sanfilippo PG;Carbonaro F;Tah V;Li YJ;Bennett SL;Craig JE;Montgomery GW;Tran-Viet KN;Brown NL;Spector TD;Martin NG;Young TL;Hammond CJ;Mackey DA
通讯作者：
Mackey DA

Regulation of Brn3b by DLX1 and DLX2 is required for retinal ganglion cell differentiation in the vertebrate retina.

DOI：
10.1242/dev.142042
发表时间：
2017-05-01
期刊：
Development (Cambridge, England)
影响因子：
0
作者：
Zhang Q;Zagozewski J;Cheng S;Dixit R;Zhang S;de Melo J;Mu X;Klein WH;Brown NL;Wigle JT;Schuurmans C;Eisenstat DD
通讯作者：
Eisenstat DD