Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA; Laboratory of Cellular and Molecular Endocrinology and Laboratory of Pharmacology and Brain Pathology, Humanitas Clinical and Research Center - IRCCS, Rozzano, Mi, Italy.
NET Service and Endocrine Oncology Bioinformatics Lab, Sheba Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Ramat Gan, Israel.
Mol Cell Endocrinol. 2021 Jan 15;520:111091. doi: 10.1016/j.mce.2020.111091. Epub 2020 Nov 26.
We recently described X-linked acrogigantism (X-LAG), a condition of early childhood-onset pituitary gigantism associated with microduplications of the GPR101 receptor. The expression of GPR101 in hyperplastic pituitary regions and tumors in X-LAG patients, and GPR101's normally transient pituitary expression during fetal development, suggest a role in the regulation of growth. Nevertheless, little is still known about GPR101's physiological functions, especially during development. By using zebrafish models, we investigated the role of gpr101 during embryonic development and somatic growth. Transient ectopic gpr101 expression perturbed the embryonic body plan but did not affect growth. Loss of gpr101 led to a significant reduction in body size that was even more pronounced in the absence of maternal transcripts, as well as subfertility. These changes were accompanied by gastrulation and hypothalamic defects. In conclusion, both gpr101 loss- and gain-of-function affect, in different ways, fertility, embryonic patterning, growth and brain development.
我们最近描述了 X 连锁肢端巨大症（X-LAG），这是一种儿童期发病的垂体巨大症，与 GPR101 受体的微重复有关。X-LAG 患者的垂体增生区域和肿瘤中 GPR101 的表达，以及 GPR101 在胎儿发育过程中正常短暂的垂体表达，表明其在生长调节中发挥作用。然而，人们对 GPR101 的生理功能仍知之甚少，尤其是在发育过程中。我们通过使用斑马鱼模型，研究了 gpr101 在胚胎发育和躯体生长过程中的作用。短暂异位表达 gpr101 会扰乱胚胎的体轴模式，但不会影响生长。gpr101 的缺失导致体型显著减小，而在没有母本转录本的情况下，这种情况更为明显，同时还伴有生育力下降。这些变化伴随着原肠胚形成和下丘脑缺陷。总之，gpr101 的功能丧失和获得以不同的方式影响生育力、胚胎模式形成、生长和大脑发育。
