Cell Fate Determination in Fetal Testes
Cell Fate Determination in Fetal Testes
批准号:
8264238
负责人:
Paul S. Cooke
金额:
$35.96万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-09-30 至 2013-08-31
中文摘要
点击翻译按钮获取中文摘要
英文摘要
A central interest in developmental, reproductive, and stem biology is how common
precursor cells acquire instruction to differentiate into specialized cell types in various
organs. Understanding how cell fates are determined not only satisfies the curiosity on
how tissues form, but also has a great implication in controlling and manipulating the
differentiation program for tissue regeneration and therapeutical purposes. The main
goal of this proposal is to understand how fetal and adult Leydig cell lineages, the
cell types responsible for masculinization and fertility of the male, are
established. Fetal and adult Leydig celis are two distinct androgen-producing celis that
appear at different developmental stages and exhibit unique morphological and
molecular characteristics. Defects in the establishment of fetal and adult Leydig cell
populations or their ability to produce hormones have a profound impact on
differentiation of male reproductive tract, spermatogenesis, and fertility. It is therefore
essential to understand how these two Leydig celi populations arise and their
differentiation is regulated. Our preliminary results suggest that fetal and adult Leydig
cells originate from a common precursor in fetal life and the hedgehog (Hh) signaling
pathway is responsible for the separation of these two Leydig celi lineages from the
common precursor population. We therefore propose to 1) investigate the effects of
ectopic activation of the Hh in the differentiation of fetal and adult Leydig cells, 2) isolate
the putative Leydig cell precursors and examine their ability to differentiate into adult
Leydig cells, and 3) examine the contribution of Gli1-positive interstitial cells to adult
Leydig cells. This application will not only provide an insight into the biological basis of
cell fate determination in testes, but will also have clinical relevance by identifying
processes susceptible to disorders of male sexual development.
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