BMP7和Notch在小鼠泌尿系统发育过程中的作用研究

发布时间：2018-02-01 00:53

本文关键词： 骨形成蛋白7 Notch 前列腺泌尿生殖系统胚胎　出处：《吉林大学》2011年博士论文　论文类型：学位论文

【摘要】：哺乳动物的泌尿生殖系统、膀胱、尿道和外生殖器从胚胎后肠尾部的泄殖腔发育而来。泌尿生殖管畸形在人类的发生率很高,而且经常伴随着泌尿外生殖器的畸形和尿道直肠隔的缺失。泌尿生殖系统的形态学发育机制还不清楚。泌尿生殖系统的发育机制、肛门直肠和生殖器官畸形的遗传原因是目前该领域研究的热点问题之一。 (1)应用骨形成蛋白7缺失转基因小鼠来研究骨形成蛋白7在小鼠泌尿生殖系统的表达、以及病理学改变。并通过骨形成蛋白7缺失和其它信号通路如wnt、wnt/pcp之间的关系,阐明骨形成蛋白7引起的小鼠泌尿生殖系统变化的机制。(2)选用三个前列腺特异的转基因小鼠系统,研究增强和缺失Notch信号对小鼠前列腺发育的影响。研究表明BMP7在泄殖腔膈的发育过程中,在泄殖腔的内胚层发育、分化过程中起着非常重要的作用。尿道和后肠的形成直接受BMP7、典型和非典型WNT信号通路调节。在人和小鼠泄殖腔内胚层发育过程中,BMP7缺失可以引起尿道和直肠不能形成、泌尿直肠畸形和尿道下裂。BMP7在泄殖腔的形态发育过程中,抑制典型Wnt信号通路、BMP7促进非典型Wnt信号通路,促进细胞的增殖和细胞的极性分化,抑制细胞的程序性死亡。此外,Notch信号通路在前列腺的发育过程中也具有相当重要的作用,它可以促进前列腺上皮细胞和间质细胞的增生、抑制上皮细胞分化;Notch信号的增强表达可以引起前列腺上皮的良性增生。
[Abstract]:Mammalian genitourinary system, bladder, urethra, and external genitalia developed from the cloacal cauda of the post-embryonic intestine. The incidence of urogenital malformations is high in humans. And often accompanied by external genitourinary malformation and the absence of urethral rectum. The mechanism of urogenital morphological development is not clear. The genetic cause of anorectal and genital malformations is one of the hot issues in this field. 1) to study the expression of bone morphogenetic protein 7 in the genitourinary system of mice with bone morphogenetic protein 7 deletion transgenic mice. And pathological changes. And the relationship between bone morphogenetic protein 7 deletion and other signaling pathways such as wntnt / pcp. To elucidate the mechanism of genitourinary system changes induced by bone morphogenetic protein 7 (BMP 7) three prostate specific transgenic mice were selected. To study the effects of enhanced and absent Notch signal on prostate development in mice. BMP7 plays an important role in the development of cloaca diaphragm and in the development and differentiation of endoderm of cloacal cavity. The formation of urethra and hindgut is directly affected by BMP7. Typical and atypical WNT signaling pathways are regulated. During the development of endoderm in human and mouse cloacal cavity, the absence of BMP7 may lead to failure of urethra and rectum. Urorectum malformation and hypospadias. BMP7 inhibits typical Wnt signaling pathway and promotes atypical Wnt signaling pathway during the development of cloaca. Promote cell proliferation and cell polarity differentiation, inhibit programmed cell death. In addition, Notch signaling pathway also plays an important role in the development of prostate. It can promote the proliferation of prostatic epithelial cells and interstitial cells and inhibit the differentiation of epithelial cells. The enhanced expression of Notch signal may lead to benign hyperplasia of prostate epithelium.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R363

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