RAPID: Physiological and molecular mechanisms that explain reproductive-female-specific skeletal growth in a highly cooperative mammal, the Damaraland mole rat

这个RAPID奖是在南非喀拉哈里沙漠对达马拉兰鼹鼠进行的一项正在进行的实验中获得的，达马拉兰鼹鼠是一种高度社会化的哺乳动物，它们合作抚养自己的孩子。目的是测试关于繁殖如何驱动女性骨骼生长和重塑的假设。将生殖雌性鼹鼠的两种骨骼（分别为腰椎和股骨）和非生殖雌性鼹鼠的相同骨骼进行骨骼生长和骨源性干细胞活性、矿化潜力、基因表达和对激素信号的反应性进行比较。该项目将提供关于激素信号和激素介导的基因表达变化如何导致骨骼生长的新信息，这与这种异常合作的哺乳动物的适应性有关。研究结果将广泛适用于理解哺乳动物骨骼重塑和生长的控制。该项目包括在南非喀拉哈里研究中心培训一名博士后和志愿者，以及在北卡罗来纳自然科学博物馆开展公共教育。该项目将为达马拉兰鼹鼠社会进化的生理和基因组目标提供新的见解。在这个群居物种的雌性中，次生骨骼生长（腰椎伸长和骨盆带变宽）是生殖活动的一个功能，导致产仔数增加。该项目将研究骨形成间充质干细胞的基因调控差异，以解释这种繁殖雌性特异性生长表型。它将验证雌激素和胰岛素样生长因子信号可以区分有生育能力的女性和没有生育能力的女性，以及经历二次生长的骨骼和没有二次生长的骨骼。干细胞基因表达和雌激素受体转录因子结合位点染色质可及性的差异将被量化。通过阐明雌性鼹鼠永久性、继发性骨骼生长的生理机制，研究结果将有助于更好地理解包括人类在内的成年哺乳动物的骨骼生长是如何被控制的。

This RAPID award takes advantage of an ongoing experiment in the Kalahari Desert of South Africa on the Damaraland mole rat, a highly social mammal that cooperatively raises its young. The goal is to test hypotheses about how breeding drives bone growth and remodeling in females. Two bones that do and do not elongate in reproductive female mole rats (lumbar vertebrae and femur, respectively), and the same bones in nonreproductive females, will be compared for bone growth and bone-derived stem cell activity, mineralization potential, gene expression, and responsiveness to hormonal signals. The project will provide new information about how hormonal signals and hormonally-mediated gene expression changes result in bone growth that is related to fitness in this unusually cooperative mammal. Results will be broadly applicable to understanding the control of skeletal remodeling and growth in mammals. The project involves training of a postdoctoral fellow and volunteers at the Kalahari Research Centre in South Africa, and public education at the North Carolina Museum of Natural Sciences. This project will provide novel insight into the physiological and genomic targets of social evolution in the Damaraland mole rat. In females of this eusocial species, secondary skeletal growth (lumbar vertebrae elongation and widening of the pelvic girdle) is a function of reproductive activity and results in increased litter sizes. The project will investigate gene regulatory differences in bone-forming mesenchymal stem cells that explain this breeding female-specific growth phenotype. It will test the hypothesis that estrogen and insulin-like growth factor signaling differentiate reproductive females and non-breeders, and bones that experience secondary growth from those that do not. Differences in stem cell gene expression and chromatin accessibility at estrogen-receptor transcription-factor binding sites will be quantified. By elucidating the physiological mechanisms underlying permanent, secondary skeletal growth in mole rat females, the results will lead to a better understanding of how skeletal growth in adult mammals, including humans, is controlled.