title: Onset of aquaporin-4 expression in the developing mouse brain.
abstract: The main water channel in the brain, aquaporin-4 (AQP4) is involved in maintaining homeostasis and water exchange in the brain. In adult mammalian brains, it is expressed in astrocytes, mainly, and in high densities in the membranes of perivascular and subpial endfeet. Here, we addressed the question how this polarized expression is established during development. We used immunocytochemistry against AQP4, zonula occludens protein-1, glial fibrillary acidic protein, and β-dystroglycan to follow astrocyte development in E15 to P3 NMRI mouse brains, and expression of AQP4. In addition we used freeze-fracture electron microscopy to detect AQP4 in the form of orthogonal arrays of particles (OAPs) on the ultrastructural level. We analyzed ventral, lateral, and dorsal regions in forebrain sections and found AQP4 immunoreactivity to emerge at E16 ventrally before lateral (E17) and dorsal (E18) areas. AQP4 staining was spread over cell processes including radial glial cells in developing cortical areas and became restricted to astroglial endfeet at P1-P3. This was confirmed by double labeling with GFAP. In freeze-fracture replicas OAPs were found with a slight time delay but with a similar ventral to dorsal gradient. Thus, AQP4 is expressed in the embryonic mouse brain starting at E16, earlier than previously reported. However a polarized expression necessary for homeostatic function and water balance emerges at later stages around and after birth.
authors.affiliation: Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Fallier-Becker
authors.affiliation: Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany.
authors.forename: Jörg P
authors.initials: JP
authors.lastname: Vollmer
authors.affiliation: Paracelsus Medical University and SCI-TReC Salzburg, Austria.
authors.forename: Hans-C
authors.initials: HC
authors.lastname: Bauer
authors.affiliation: Department of Neurosurgery, University of Tübingen, Tübingen, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: Noell
authors.affiliation: Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.affiliation: Institute of Anatomy, University of Tübingen, Tübingen, Germany. Electronic address: mack@anatu.uni-tuebingen.de.
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Mack
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051401:Aquaporin 4 / Q000378:metabolism* / Q000648:ultrastructure; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D049030:Dystroglycans / Q000378:metabolism; D004622:Embryo, Mammalian; D005614:Freeze Fracturing; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D049030:Dystroglycans
keywords: Freeze-fracture; GFAP; Glia; Homeostasis; Orthogonal arrays of particles