functions of zebrafish hif1α and hif3α gene in inner ear and blood vessels development
| Autor: | Huay-Win Young, 楊惠雯 |
|---|---|
| Rok vydání: | 2003 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 91 Recently, a novel bHLH-PAS protein family were revealed to have important roles in vertebrate development, including the aryl hydrocarbon receptor nuclear translocator (ANRT) and its associate factor, hypoxia-inducible factor alpha subunit (HIF a). There are multiple forms of HIF a subunits that have been identified in vertebrate, including the HIF-1 a,HIF-2 a and HIF-3 a. The unstable HIF a subunits act as intracellular oxygen sensor and it is stabilized by oxygen deficiency. Once being activated by hypoxia signaling, HIF a subunit associates with ARNT to form a heterodimeric complex and binds to the hypoxia-response elements to stimulate transcriptions of target genes. Previously, Two forms of HIF a subunit cDNA, hif1α and hfi3α, were cloned from zebrafish cDNA library. The spatiotemporal expression pattern of hif1α and hfi3α in the developing embryo was revealed by whole mount RNA in situ hybridization. It appears that these two genes express with overlap in diencephalons, olfactory placode, lateral line placode and otic placode during 24~48 hpf stage. It suggests that these hypoxia inducible factors play important roles in sensory organs development. In this study, the function of HIF1α and HIF3α in fish sensory organs development is revealed by gene knock-down via microinjection of gene-specific morpholino-oligonucleotides. The hif1α- and hif3α-specific antisense morpholino-integrated oligonucleotides (MO) was injected into embryos at 1-2 cell stage. We found that both gene-specific MO had strong effects in embryonic development, such as anatomical defects in the inner ear (size and shape of otoliths, formation of the semicircular canals), small head, nasal pit and eyes, malformation of inner ears and liver. In this study, we investigate the functions of hif1α and hif3α induced abnormal inner ear and vessels. The expression pattern of markers otx1, lfabp, dlx3, and bmp4 were all disturbed by the hif1α- and hif3α-specific MO injection. It suggests that hif1α and hif3α and their related signaling pathway play important roles in inner ear and vascular development. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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