Cell Fate Determination in Fetal Testes

发育、生殖和干生物学的核心兴趣是如何普遍 前体细胞获得指令以分化成各种类型的特化细胞。 机关了解细胞命运是如何决定的，不仅满足了人们对 组织是如何形成的，而且在控制和操纵组织方面也有很大的意义。 用于组织再生和治疗目的的分化程序。主要 这项建议的目的是了解胎儿和成人间质细胞谱系， 负责男性化和男性生育力的细胞类型是 确立了习胎儿和成人间质细胞是两种不同的产生雄激素的细胞， 出现在不同的发育阶段，并表现出独特的形态和 分子特征胎儿和成人睾丸间质细胞建立的缺陷 人口或他们产生激素的能力对人类的健康有着深远的影响。 雄性生殖道的分化、精子发生和生育力。因此 了解这两个Leydig细胞群是如何产生的， 分化是有规律的。我们的初步结果表明，胎儿和成人Leydig 细胞起源于胎儿生命和刺猬（Hh）信号的共同前体 通路负责将这两种Leydig细胞谱系从 共同的前体人口。因此，我们建议：1）调查 Hh在胎儿和成人Leydig细胞分化中的异位激活，2）分离 假定Leydig细胞前体并检测它们分化成成体的能力 Leydig细胞，以及3）检查Gli1阳性间质细胞对成体的贡献。 睾丸间质细胞。这一应用不仅将提供一个深入了解的生物学基础， 细胞命运的决定，但也将有临床意义，通过确定 易受男性性发育障碍影响的过程。

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.