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Function of albinism gene oca2 in non-melanocyte cell development

白化病基因oca2在非黑素细胞发育中的作用

基本信息

批准号：
10450112
负责人：
Cynthia D COOPER
金额：
$ 7.65万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-14 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10450112
关键词：
Address Albinism Biological Assay Biological Models Birth Cell Count Cell Death Cell Proliferation Cell physiology Cells Cessation of life Chick Clutch Size Collection Color Data Defect Development Disease Embryo Event Fertilization Gene Expression Genes Goals Hand Hearing Hour Human Hypopigmentation In Situ Hybridization Individual Laboratories Larva Lead Light Melanins Methods Modeling Molecular Mutate Nerve Nerve Tissue Neural Crest Neural Crest Cell Oculocutaneous Albinism Optics Patients Pattern Pigments Public Health Publishing Research Resources Role Sample Size Sampling Sensory Shapes Siblings Side Silver Skin Specific qualifier value System Systems Development Testing Tissues Vertebrates Vision Visual Waardenburg syndrome Work Zebrafish cell type egg experimental study fovea centralis gene function hearing impairment in vivo Model insight loss of function loss of function mutation melanocyte melanoma migration mutant novel pleiotropism precursor cell prevent relating to nervous system side effect single-cell RNA sequencing skin color skin organogenesis transcriptome sequencing undergraduate research visual processing zygote

项目摘要

Project summary Loss of function mutations in the oculocutaneous albinism 2 (oca2) gene not only lead to defects in black pigment (melanin) synthesis important for skin color, but also increase the chances of developing “side” or “pleiotropic” effects. Some examples of pleiotropic effects include deficiencies in sensory or neural system development, as well as embryonic death depending on the identity of the mutated gene. Although pleiotropic effects are commonly observed in humans with hypopigmentation disorders like Waardenburg Syndrome and albinism, the underlying mechanisms are poorly understood primarily due to low sample size. Because pigment cells are easily viewed through transparent skin and eggs can be collected in high numbers year round, we propose to use zebrafish silver cells to better understand how pleiotropic effects arise. When oca2 is mutated, zebrafish larvae continue to make the correct number of black pigment cells, melanocytes, but melanin synthesis is severely decreased. Conversely, silver pigment cells do not express oca2, but are increased in number at stages following specification from neural crest. Using oca2 mutant iridophores as a model, we will address the following R03 specific aims: 1) Determine the iridophore developmental stages impacted by oca2 function. With aim 1 experiments, we will retest the role of oca2 in iridophore specification and examine iridophore development at multiple, additional stages including proliferation, differentiation and survival – all cellular events that could impact cell number; 2) Determine if oca2 directly or indirectly regulates iridophore number. Using our unique collection of melanocyte mutants, we will determine if oca2 directly (cell-autonomously) or indirectly (non- cell autonomously) regulates iridophore development. In additional experiments, we will conduct pilot [bulk and single cell RNA-Seq] analysis to determine if these methods can provide insight into oca2’s autonomous versus non-autonomous role during iridophore development. Specifically, these RNA-seq data will be analyzed to determine whether changes in the expression of intrinsic or extrinsic genes important for iridophore development occur with oca2 loss of function. Once these experiments are complete, we will have a characterized model for testing oca2 function in pleiotropic effects and a substantial amount of preliminary data for formulating hypotheses appropriate for R01 level research aimed at elucidating mechanistic connections between melanocytes/melanin and hearing/visual/skin system development in humans.

项目总结

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Zebrafish Syndromic Albinism Models as Tools for Understanding and Treating Pigment Cell Disease in Humans.

DOI：
10.3390/cancers14071752
发表时间：
2022-03-30
期刊：
Cancers
影响因子：
5.2
作者：
Neuffer SJ;Cooper CD
通讯作者：
Cooper CD

AP-3 complex subunit delta gene, ap3d1, regulates melanogenesis and melanophore survival via autophagy in zebrafish (Danio rerio).

DOI：
10.1111/pcmr.13055
发表时间：
2022-09
期刊：
PIGMENT CELL & MELANOMA RESEARCH
影响因子：
4.3
作者：
Neuffer, Sam J.;Beltran-Cardona, David;Jimenez-Perez, Kevin;Clancey, Lauren F.;Brown, Alexander;New, Leslie;Cooper, Cynthia D.
通讯作者：
Cooper, Cynthia D.