| 项目编号: | 1600920
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| 项目名称: | DISSERTATION RESEARCH: Mutant models reveal latent developmental potential with roles in evolutionary change |
| 作者: | James Hanken
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| 承担单位: | Harvard University
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| 批准年: | 2016
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| 开始日期: | 2016-07-01
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| 结束日期: | 2018-06-30
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| 资助金额: | 18867
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Biological Sciences - Environmental Biology
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| 英文关键词: | p-d
; limb
; development
; researcher
; such research
; simple genetic change
; model species
; fin
; formation
; evolution
; additive phenotypic change
; research opportunity
; zebrafish
; genetic change
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| 英文摘要: | This project will investigate the genetic factors that cause elaborated bone pattern in fish fins. Bone pattern elaboration results from increases in bone numbers and connections, and such research is important for understanding processes of both evolution and development. In evolution, increase in the number of bones arranged end-to-end helped transform fins into limbs and aided the colonization of land by extinct vertebrates. In development, normal function and movement depends upon formation of the proper bone numbers and connections, and defective development can lead to severe impairment. Currently, the mechanisms that led to elaboration of the fin skeleton to form limbs are unknown. To identify the genetic factors involved, the researchers will study strains of the model species, zebrafish, that have genetic changes that result in the formation of new fin bones. They will also investigate naturally occurring variation in two species, gar and bowfin, that have different numbers of bones extending from the shoulder. These complementary approaches will reveal the mechanisms regulating growth and formation of the skeleton of fins and limbs, and show how simple genetic changes can lead to the formation of limbs from fins. Understanding the mechanisms of bone pattern elaboration and development has implications for human health and developmental abnormalities, and may provide clues for the evolution of life on land. Additionally, the project will provide research opportunities for Native American undergraduates.
While tetrapod vertebrates have increased the number of bones along the proximo-distal (P-D) axis of the limb, teleost fishes such as the zebrafish have reduced the pectoral fin skeleton; only a single long bone is found along the P-D axis. The researchers performed a forward mutagenesis screen in zebrafish and isolated a novel mutant that forms supernumerary bones along the P-D axis of the fin through a process similar to that seen in the development of tetrapod limbs. The proposed research will extend results from mutant analysis to natural populations to determine if the mutation is producing supernumerary bones by activating ancestral genetic mechanisms. Transcriptome profiling by RNA sequencing will be used to compare gene-expression levels in the developing pectoral fins of wild-type and mutant zebrafish, as well as two species that exhibit natural variation in P-D axis elaboration. This analysis will reveal patterns of differential gene expression that correlate with P-D axis elaboration. Differentially expressed genes will be tested in the zebrafish to determine if their modified expression has an effect on fin morphology. This study will elucidate how additive phenotypic changes arise in development and identify candidate pathways by which additional fin/limb bones are formed in both evolution and disease. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/91918
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| Appears in Collections: | 全球变化的国际研究计划
科学计划与规划
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| Recommended Citation: | |
James Hanken. DISSERTATION RESEARCH: Mutant models reveal latent developmental potential with roles in evolutionary change. 2016-01-01.
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