Functions of Hypoxia-Inducible Factor HIF 1Alpha and HIF 3Alpha in Zebrafish Cranial Cartilages and Sense Organs Development

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基本資料

Project title

Code/計畫編號

NSC90-2313-B019-030

Translated Name/計畫中文名

低氧誘發蛋白HIF 1Alpha與HIF 3Alpha對斑馬魚頭部軟骨與感覺神經系統發育的影響

Project Coordinator/計畫主持人

Chin-Hwa Hu

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Department of Bioscience and Biotechnology

Website

https://www.grb.gov.tw/search/planDetail?id=670383

Year

2001

Start date/計畫起

01-08-2001

Expected Completion/計畫迄

01-07-2002

Bugetid/研究經費

904千元

ResearchField/研究領域

生物科學

生物胚胎的發育過程是經由一個嚴密調控的細胞程式來控制胚胎內細胞的分裂與分化的進行，其中細胞核內的許多DNA辨識蛋白在胚胎發育過程中直接參與了各階段的基因的調控工作。這些常見的基因調控蛋白包括了各種的Homeobox protein、basic-helix-loop-helix (bHLH) protein、Zinc finger DNA binding protein、Basic leucine zipper protein等等。先前本實驗室對斑馬魚的一組bHLH-PAS蛋白進行了選殖及表現的研究工作，其中低氧誘發蛋白HIF 1alpha與HIF 3alpha在細胞遇到缺氧的情況時會與ARNT結合成安定的基因轉錄子，進而調控下游基因的表現以調適細胞缺氧的環境。在實驗中，我們觀察到斑馬魚細胞HIF 1alpha與HIF 3alpha基因在胚胎發育時，首先會在初期呈現非專一性的廣泛表現，隨後逐漸在頭部的軟骨組織、感覺器官的基板(包括嗅基板、耳基板以及側線基板)以及後腦等部位出現明顯而專一的表現。這些結果顯示HIF 1alpha與HIF 3alpha可能在頭部的感覺器官與頭顱的發育上扮演了重要的功能。在這項計畫中，我們利用HIF 1alpha與HIF 3alpha專一性的Morpholino (MO)以顯微注射的方式注入1-2 cell stage的胚胎中以干擾正常胚胎內HIF 1alpha與HIF 3alpha的下游基因的調控機制，續以Alcine blue染色的方法觀察頭部軟骨組織的發育。我們的實驗結果顯示了HIF 1alpha與HIF 3alpha-specific MO嚴重干擾了頭骨的發育；此外，HIF 1alpha與HIF 3alpha-specific MO亦減低dHAND與hoxa2基因的表現，顯示低氧誘發子HIF 1alpha與HIF 3alpha確實參與了頭骨的發育機制。 Recently, a novel bHLH-PAS protein family were revealed to act important roles in vertebrate development. Members of bHLH-PAS proteins include aryl hydrocarbon receptor (AHR) and its associate factor (ARNT), SIM, PER, CLOCK, and hypoxia-inducible factor, HIFs. In previous study, we have identified a group of bHLH-PAS factors from zebrafish and they all exhibit specific expression pattern in the developing embryos. For instance, the mRNA of hypoxia inducible factor HIF 1alpha and HIF 3alpha were expressed in the hindbrain, developing cranial cartilage, pharyngeal arches, olfactory placed, lateral line placode and otic placode. It suggests that these hypoxia inducible factors play important roles in fish development. In this study, we focus on the functions of hypoxia inducible factors in fish cranial cartilage and sensory organs development. The HIF 1alpha and HIF 3alpha-specific morpholino oligonucleotides were injected into fertilized eggs at 1-2 cell stages. The head cartilage development in these disrupted embryos was examined by Alcine blue stain. It appears that the formation of neurocranium and pharyngeal arches was severe disrupted in the HIF 1alpha and HIF 3alpha-MO injected embryos. The expression of dHAND and hoxa2 were also reduced in these MO-treated embryos. It suggests that HIF 1alpha and HIF 3alpha genes act important roles in head skeleton development.

Keyword(s)

斑馬魚
軟骨
發育
神經系統
低氧誘發蛋白
Zebrafish
Cartilage
Development
Nervous system
Hypoxia-inducible factor
HIF 3α
HIF 1α

DSpace CRIS

Functions of Hypoxia-Inducible Factor HIF 1Alpha and HIF 3Alpha in Zebrafish Cranial Cartilages and Sense Organs Development

基本資料

Description