Corkins Mark E, Romero-Mora Adrian, Achieng MaryAnne A, Lindström Nils O, Miller Rachel K
Department of Pediatrics, Pediatric Research Center, UTHealth McGovern Medical School, Houston, Texas 77030.
Department of Cell, Developmental & Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY. 10029.
bioRxiv. 2025 Jan 28:2025.01.13.632850. doi: 10.1101/2025.01.13.632850.
The mammalian kidney develops in three sequential stages referred to as the pronephros, mesonephros, and metanephros, each developing from the preceding form. All three phases of kidney development utilize epithelized tubules called nephrons, which function to take in filtrate from the blood or coelom and selectively reabsorb solutes the organism needs, leaving waste products to be excreted as urine. The pronephros are heavily studied in aquatic organisms such as zebrafish and Xenopus, as they develop quickly and are functional. The metanephros is a preferred mammalian kidney model, as it best recapitulates human disease. However, very little is known about the mesonephric stage of kidney development in any organism. The pronephros extend to form the mesonephric duct, which ultimately develops into the Wolffian duct in male amniotes. Meanwhile, in organisms that lay their eggs in aquatic environments, the mesonephric kidney is the final form that is generated. Therefore, further understanding of the development and physiology of these kidneys will provide insight into the urogenital system as well as its evolutionary conservation. To gain a better understanding of its structure and cell types, we analyzed the developing mesonephros by in situ and single-cell mRNA sequencing of cells the that make up the developing mesonephros. By comparing these data to those published for the pronephros and mammalian metanephros, we were able to evaluate nephron conservation between the three kidney stages.
哺乳动物的肾脏发育经历三个连续阶段,即前肾、中肾和后肾,每个阶段都由前一个阶段发育而来。肾脏发育的所有三个阶段都利用称为肾单位的上皮化小管,其功能是从血液或体腔中摄取滤液,并选择性地重新吸收生物体所需的溶质,将废物作为尿液排出。前肾在斑马鱼和非洲爪蟾等水生生物中得到了深入研究,因为它们发育迅速且具有功能。后肾是首选的哺乳动物肾脏模型,因为它最能重现人类疾病。然而,对于任何生物体肾脏发育的中肾阶段却知之甚少。前肾延伸形成中肾管,在雄性羊膜动物中最终发育为沃尔夫管。同时,在将卵产在水生环境中的生物体中,中肾是最终形成的肾脏形式。因此,进一步了解这些肾脏的发育和生理学将有助于深入了解泌尿生殖系统及其进化保守性。为了更好地了解其结构和细胞类型,我们通过对构成发育中的中肾的细胞进行原位和单细胞mRNA测序来分析发育中的中肾。通过将这些数据与已发表的前肾和哺乳动物后肾的数据进行比较,我们能够评估三个肾脏阶段之间肾单位的保守性。