The Journal of Neuroscience, March 21, 2007, 27(12):3139-3147; doi:10.1523/JNEUROSCI.5151-06.2007
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Development/Plasticity/Repair
Asymmetric Distribution of Prickle-Like 2 Reveals an Early Underlying Polarization of Vestibular Sensory Epithelia in the Inner Ear
Michael R. Deans,1 *
Dragana Antic,2,3 *
Kaye Suyama,2
Matthew P. Scott,2
Jeffrey D. Axelrod,3 ** and
Lisa V. Goodrich1 **
1Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, 2Departments of Developmental Biology, Genetics, and Bioengineering, Howard Hughes Medical Institute, and 3Department of Pathology, Stanford University School of Medicine, Stanford, California 94305
Correspondence should be addressed to Lisa V. Goodrich, Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115. Email: Lisa_Goodrich{at}hms.harvard.edu
Vestibular hair cells have a distinct planar cell polarity (PCP) manifest in the morphology of their stereocilia bundles and the asymmetric localization of their kinocilia. In the utricle and saccule the hair cells are arranged in an orderly array about an abrupt line of reversal that separates fields of cells with opposite polarity. We report that the putative PCP protein Prickle-like 2 (Pk2) is distributed in crescents on the medial sides of vestibular epithelial cells before the morphological polarization of hair cells. Despite the presence of a line of polarity reversal, crescent position is not altered between hair cells of opposite polarity. Frizzled 6 (Fz6), a second PCP protein, is distributed opposite Pk2 along the lateral side of vestibular support cells. Similar to Pk2, the subcellular localization of Fz6 does not differ between cells located on opposite sides of the line of reversal. In addition, in Looptail/Van Gogh-like2 mutant mice Pk2 is distributed asymmetrically at embryonic day 14.5 (E14.5), but this localization is not coordinated between adjacent cells, and the crescents subsequently are lost by E18.5. Together, these results support the idea that a conserved PCP complex acts before stereocilia bundle development to provide an underlying polarity to all cells in the vestibular epithelia and that cells on either side of the line of reversal are programmed to direct the kinocilium in opposite directions with respect to the polarity axis defined by PCP protein distribution.
Key words: planar cell polarity; Prickle; hair cell; vestibular; Looptail; line of reversal
Received Nov. 28, 2006;
revised Feb. 8, 2007;
accepted Feb. 9, 2007.
Correspondence should be addressed to Lisa V. Goodrich, Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115. Email: Lisa_Goodrich{at}hms.harvard.edu
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