title: Ciliogenesis in normal human kidney development and post-natal life.
abstract: Ciliogenesis in developing and post-natal human kidneys appears to influence cell proliferation and differentiation, apico-basal cell polarity, and tubular lumen formation. We have analyzed the appearance of primary cilia and differentiation of kidney cells in ten human conceptuses aged 6-22 weeks and in one 5-year-old kidney, using a double immunofluorescence labeling technique for α-tubulin, γ-tubulin, Oct-4, and Ki-67 and by electron microscopy. Immature forms of nephrons and ampullae were characterized by intense cell proliferation, which subsequently decreased during development. Primary cilia appeared on the surfaces of non-proliferating cells in developing nephrons, gradually increasing in length from 0.59 μm in renal vesicles to 0.81 μm in the S-forms of nephrons, ultimately reaching 3.04 μm in length in mature fetal and post-natal nephrons. Ciliary length increased from 0.59 μm in ampullae to 1.28 μm in post-natal collecting tubules. Mesenchymal to epithelial transformation of kidney cells coincided with the appearance of apico-basal polarity, both gap and tight junctions, and lumen formation. Up-regulation of Oct-4 expression correlated with the onset of kidney cell differentiation. Our results demonstrate the importance of proper primary cilia lengthening and Oct-4 expression for the normal development of fetal and post-natal kidneys and of apico-basal polarity for normal tubular lumen formation. Disturbances in these processes are associated with ciliopathies.
authors.affiliation: Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Šoltanska 2, 21000 Split, Croatia. msb@mefst.hr
authors.forename: Mirna
authors.initials: M
authors.lastname: Saraga-Babić
authors.forename: Katarina
authors.initials: K
authors.lastname: Vukojević
authors.forename: Ivana
authors.initials: I
authors.lastname: Bočina
authors.forename: Kristina
authors.initials: K
authors.lastname: Drnašin
authors.forename: Marijan
authors.initials: M
authors.lastname: Saraga
mesh_terms: D000367:Age Factors; D016764:Cell Polarity; D049109:Cell Proliferation; D002675:Child, Preschool; D002923:Cilia / Q000737:chemistry / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D005865:Gestational Age; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D007668:Kidney / Q000737:chemistry / Q000196:embryology* / Q000254:growth & development* / Q000648:ultrastructure; D007684:Kidney Tubules / Q000196:embryology / Q000254:growth & development; D008854:Microscopy, Electron; D009024:Morphogenesis; D009399:Nephrons / Q000196:embryology / Q000254:growth & development; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D014404:Tubulin / Q000032:analysis
chemical_list: D019394:Ki-67 Antigen; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D014404:Tubulin