Is sexual development conserved between birds and mammals?
Is sexual development conserved between birds and mammals?
批准号:
BB/E015425/2
负责人:
Michael Clinton
金额:
$49.57万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2008
资助国家:
英国
项目状态:
已结题
起止时间:
2008 至 --
中文摘要
在世纪中期,阿尔弗雷德·约斯特进行了一系列实验,他通过手术切除了早期雄性兔子胚胎的睾丸,并将睾丸移植到早期雌性兔子胚胎中。雄性胎儿发育成看起来像雌性的兔子,雌性胎儿发育成看起来像雄性的兔子。这导致了哺乳动物性发育是一个三步过程的模型:第一步是在受精时建立染色体性别,第二步是建立主要的性特征(睾丸和卵巢),第三步是第二性征的发展,这取决于性腺分泌的激素。这个模型的核心是这样一个概念,即哺乳动物胎儿在发育早期经历了一个性“冷漠”时期,成年后的性外观取决于形成的性腺类型。这个模型现在被广泛接受,并被认为适用于所有脊椎动物物种。然而,“冷漠”胎儿的基本概念和第二性征对性腺产物的依赖性最近受到了挑战。已经报道了植入前雄性和雌性哺乳动物胚胎的生长速率和基因表达模式的差异,并且已经提出斑胸草雀大脑的性别分化不依赖于性腺激素。我们最近发现了似乎是半公半母的鸟类。我们对这些鸟类的分析表明,鸟类的性别决定和性发育并不遵循哺乳动物的模式。我们的证据表明,鸟类的第二性征不依赖于性腺的性质形成,并建议一个内在的细胞性别身份。此外,我们还确定了一种新的女性特异性转录本,在整个发育过程中在所有女性细胞中表达,最显着的是在所谓的“冷漠”发育阶段。这就提出了一种可能性,即在受精和性腺决定和/或第二性征中赋予鸟类细胞的固有性别身份在很大程度上是这种细胞自主性别身份的结果。我们将通过产生由雄性和雌性细胞和/或组织的混合物组成的鸟类来研究这种可能性。我们将监测异性细胞的存在如何影响组织/生物体的表型,以及细胞环境如何影响这些细胞的功能。我们将生成三个独立的模型系统来解决这些问题:1.adult由遗传雄性和遗传雌性细胞组成的鸟类,2。含有由遗传雄性和遗传雌性细胞组成的性腺的胚胎,以及3种转基因动物,其中假定的性别决定基因用于产生具有睾丸的遗传雌性和具有卵巢的遗传雄性。我们相信,这项研究将确定鸟类性发育的各个方面是细胞自主的。如果是这样的话,这将需要重新评估所有脊椎动物性别分化的既定概念,也将支持性别分化的各个方面是独立于哺乳动物性腺分泌的论点。
英文摘要
In the mid-twentieth century, Alfred Jost performed a series of experiments where he surgically removed the testes from early male rabbit fetuses and also transplanted testes into early female rabbit fetuses. The male fetuses developed into rabbits that looked female and the female fetuses developed into rabbits that appeared to be males. This led to the model that mammalian sexual development is a three step process: the first is the establishment of chromosomal sex at fertilisation, the second is the establishment of the primary sexual characteristics (testes and ovaries), and the third is development of the secondary sexual characteristics which are dependent upon hormones secreted by the gonads. Central to this model is the concept that the mammalian fetus goes through a sexually 'indifferent' period early in development and that the adult sexual appearance depends on the type of gonad formed. This model is now widely accepted and is considered to apply to all vertebrate species. However, the basic concept of the 'indifferent' fetus and the dependence of secondary sexual characteristics on gonadal products have recently been challenged. Differences in the growth rates and gene expression patterns of pre-implantation male and female mammalian embryos have been reported, and it has been proposed that sexual differentiation of the zebra finch brain is not dependent on gonadal hormones. We have recently identified birds that seem to be half male and half female. Our analyses of these birds suggests that sex-determination and sexual development in birds does not follow the mammalian model. Our evidence indicates that the secondary sexual characteristics in birds do not depend on the nature of the gonads formed and suggests an inherent cellular sex identity. In addition, we have also identified a novel female-specific transcript that is expressed in all female cells throughout development, most significantly during the supposedly 'indifferent' phase of development. This raises the possibility that an inherent sex identity is conferred on avian cells at fertilisation and gonadal determination and/or the secondary sexual characteristics are largely a result of this cell autonomous sex identity. We will investigate this possibility by generating birds that are composed of mixtures of male and female cells and/or tissues. We will monitor how the presence of cells of the opposite sex affects the phenotype of the tissue/organism, and how the cellular environment affects the function of these cells. We will generate three independent model systems to address these questions: 1.adult birds composed of genetically male and genetically female cells, 2. embryos containing gonads composed of genetically male and genetically female cells, and, 3 transgenic animals where putative sex-determining genes are used to generate genetic females with testes and genetic males with ovaries. We believe that this research will establish that aspects of sexual development in birds are cell autonomous. If so, this would necessitate a re-evaluation of the established concept of sex differentiation in all vertebrates and would also support the contention that aspects of sex differentiation are independent of gonadal secretions in the mammal.
期刊论文(9)
专著(0)
科研奖励(0)
会议论文
Heat shock induces interferon-TAU gene expression by in vitro-produced bovine blastocysts.
热休克诱导体外产生的牛囊胚表达干扰素-TAU 基因。
DOI:
10.1111/aji.12131
发表时间:
2013
期刊:
1989)
影响因子:
--
作者:
[Hickman CF]
通讯作者:
Hickman CF
DOI:
10.1371/journal.pone.0002978
发表时间:
2008-08-20
期刊:
PLOS ONE
影响因子:
3.7
作者:
[Loi, Pasqualino, Matsukawa, Kazutsugu, Ptak, Grazyna, Clinton, Michael, Fulka, Josef, Jr., Nathan, Yehudith, Arav, Amir]
通讯作者:
Arav, Amir
DOI:
10.1007/s10577-011-9257-9
发表时间:
2012-01-01
期刊:
CHROMOSOME RESEARCH
影响因子:
2.6
作者:
[Clinton, M., Zhao, D., McBride, D.]
通讯作者:
McBride, D.
Sex-determining mechanisms in the chick
-
批准号:BB/N018672/1
-
项目类别:Research Grant
-
资助金额:$57.9万
-
财政年份:2017
-
负责人:Michael Clinton
-
依托单位:
Developmental consequences and molecular basis of cell-autonomous sex identity in the chicken
-
批准号:BB/H012486/1
-
项目类别:Research Grant
-
资助金额:$85.75万
-
财政年份:2010
-
负责人:Michael Clinton
-
依托单位:
Is sexual development conserved between birds and mammals?
-
批准号:BB/E015425/1
-
项目类别:Research Grant
-
资助金额:$82.36万
-
财政年份:2007
-
负责人:Michael Clinton
-
依托单位:
国内基金
海外基金
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