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

这个RAPID奖利用了在南非喀拉哈里沙漠正在进行的一项关于达马拉兰鼹鼠的实验，达马拉兰鼹鼠是一种高度社会化的哺乳动物，合作抚养它的幼崽。其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。两个骨骼，做和不延长生殖雌性鼹鼠（腰椎和股骨，分别），在非生殖女性相同的骨骼，将比较骨生长和骨源性干细胞活性，矿化潜力，基因表达，和激素信号的反应。该项目将提供有关激素信号和神经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了解哺乳动物骨骼重塑和生长的控制。该项目包括在南非卡拉哈里研究中心培训一名博士后研究员和志愿人员，以及在北卡罗来纳州自然科学博物馆开展公共教育。该项目将提供新的洞察力的生理和基因组目标的社会进化在达马拉兰鼹鼠。在这一真社会性物种的雌性中，次级骨骼生长（腰椎伸长和骨盆带加宽）是生殖活动的函数，并导致窝仔数增加。该项目将调查基因调控的差异，在骨形成间充质干细胞，解释这种繁殖女性特异性生长表型。它将测试的假设，雌激素和胰岛素样生长因子信号区分生殖女性和非育种，和骨骼的经验，从那些不二次生长。将对干细胞基因表达和雌激素受体转录因子结合位点处染色质可及性的差异进行定量。通过阐明潜在的生理机制永久性，二次骨骼生长在鼹鼠女性，结果将导致更好地了解骨骼生长在成年哺乳动物，包括人类，是如何控制的。

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.