title: Role of Prox1 in the Transforming Ascending Thin Limb of Henle's Loop during Mouse Kidney Development.
abstract: The homeobox transcription factor Prox1 is critical to the development of many embryonic organs and tissues, although current understanding of its expression in the developing renal medulla is limited. We examined the functional role of Prox1 during mouse kidney development with particular emphasis on the developing loop of Henle. Our data show that Prox1 is expressed in the transdifferentiating region from the NKCC2-positive thick ascending limb, into the CLC-K1-positive ascending thin limb of Henle's loop beginning at embryonic day 18. From 1 to 14 days of age, Prox1-positive cells gradually disappeared from the papillary tip, and remained in the initial part of inner medulla after 21 days. In this transforming area, no Prox1 was observed in cells undergoing apoptosis but was expressed strongly in the remaining cells, which differentiated into ascending thin limb epithelial cells. In vitro and in vivo approaches showed that Prox1 expression increases where the osmolality is near optimal range, but decreases at below- or above-optimal ranges. Renal hypoosmolality induced by furosemide (NKCC2 inhibitor) inhibited Prox1 expression and delayed maturation of the ascending limb of Henle's loop. Together, these studies suggest that Prox1 appears to be a critical stage specific regulator of specifying ascending thin limb cell fate and that its expression is regulated by osmolality.
authors.affiliation: Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Wan-Young
authors.initials: WY
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Nam
authors.affiliation: Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: A-Rum
authors.initials: AR
authors.lastname: Choi
authors.affiliation: Division of Nephrology, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Korea.
authors.forename: Hyang
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yong-Kyun
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hak-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D018398:Homeodomain Proteins / Q000502:physiology*; D007679:Kidney Medulla / Q000196:embryology*; D008138:Loop of Henle / Q000196:embryology*; D051379:Mice; D009994:Osmolar Concentration; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein