Differential RA responsiveness directs formation of functionally-distinct spermatogonial populations at the initiation of spermatogenesis in the mouse

Author:

Velte Ellen K.1,Niedenberger Bryan A.1,Serra Nicholas D.1,Singh Anukriti2,Roa-DeLaCruz Lorena2,Hermann Brian P.2,Geyer Christopher B.13ORCID

Affiliation:

1. Departments of Anatomy & Cell Biology in the Brody School of Medicine, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA

2. Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA

3. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA

Abstract

In the mammalian testis, sustained spermatogenesis relies on spermatogonial stem cells (SSCs); their progeny remain as stem cells (self-renewal) or proliferate and differentiate to enter meiosis in response to retinoic acid (RA). Here, we sought to uncover elusive mechanisms regulating a key switch fundamental to spermatogonial fate, the capacity of spermatogonia to respond to RA. Using the developing mouse testis as a model, we found that spermatogonia and precursor prospermatogonia exhibit a heterogeneous capacity to respond to RA with at least two underlying causes. First, progenitor spermatogonia are prevented from responding to RA by catabolic activity of ‘cytochrome P450 family 26’ (CYP26) enzymes. Second, a smaller subset of undifferentiated spermatogonia enriched for SSCs exhibit catabolism-independent RA-insensitivity. Moreover, for the first time, we observed that precursor prospermatogonia are heterogeneous and comprised of subpopulations which exhibit the same differential RA responsiveness found in neonatal spermatogonia. We propose a novel model by which mammalian prospermatogonial and spermatogonial fates are regulated by intrinsic capacity to respond (or not) to the differentiation signal provided by RA prior to and concurrent with the initiation of spermatogenesis.

Funder

National Institutes of Health

National Science Foundation

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3