Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury.
We reported previously that astroglia cultured from aquaporin-4-deficient (AQP4-/-) mice migrate more slowly in vitro than those from wild-type (AQP4+/+) mice (J. Cell Sci. 2005;118, 5691-5698). Here, we investigate the migration of fluorescently labeled AQP4+/+ and AQP4-/- astroglia after implantation into mouse brains in which directional movement was stimulated by a planar stab wound 3 mm away from the axis of the injection needle. Two days after cell injection we determined the location, elongation ratio, and orientation of labeled cells. Migration of AQP4+/+ but not AQP4-/- cells toward the stab was greater than away from the stab. AQP4+/+ astroglia moved on average 1.5 mm toward the stab compared with 0.6 mm for AQP4-/- cells. More than 25% of the migrating AQP4+/+ cells but <3% of AQP4-/- cells appeared elongated (axial ratio>2.5). In transwell assays, AQP4+/+ astroglia migrated faster than AQP4-/- cells in a manner dependent on pore size. At 8 h, approximately 50% of AQP4+/+ cells migrated through 8-microm diameter pores, whereas equivalent migration of AQP4-/- cells was found for 12-microm diameter pores. These results provide in vivo evidence for AQP4-dependent astroglial migration and suggest that modulation of AQP4 expression or function might alter glial scarring.
Auguste
Kurtis I
KI
Department of Medicine and Physiology, University of California, San Francisco, San Francisco, CA, USA.
Jin
Songwan
S
Uchida
Kazunori
K
Yan
Donghong
D
Manley
Geoffrey T
GT
Papadopoulos
Marios C
MC
Verkman
A S
AS
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000502:physiology*; D001253:Astrocytes / Q000166:cytology*; D001921:Brain / Q000166:cytology*; D002465:Cell Movement; D002478:Cells, Cultured; D005453:Fluorescence; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4