Prickle1 regulates neurite outgrowth of apical spiral ganglion neurons but not hair cell polarity in the murine cochlea

• Published in: PloS one Vol. 12; no. 8; p. e0183773
• Main Authors: Yang, Tian, Kersigo, Jennifer, Wu, Shu, Fritzsch, Bernd, Bassuk, Alexander G
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.08.2017; Public Library of Science (PLoS)
• Subjects: Adaptor Proteins, Signal Transducing - physiology; Animals; Axonogenesis; Biology; Biology and Life Sciences; Cell Polarity - physiology; Cochlea; Cochlea - cytology; Cochlear nuclei; Defects; Dishevelled protein; Ganglia; Gene expression; Genetic aspects; Genomics; Hair; Hair cells; Hair cells (Sensory receptors); Hair Cells, Auditory - cytology; Kinases; LIM Domain Proteins - physiology; Localization; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Electron, Scanning; Mutants; Mutation; Neurites; Neurons; Neurons - cytology; Neurosciences; Nuclei; Organ of Corti; Outer hair cells; pax2 protein; Pediatrics; Physiological aspects; Polarity; Proteins; Research and Analysis Methods; Spiral ganglion; Spiral Ganglion - cytology; Staining; United States; Iowa City Iowa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0183773

In the mammalian organ of Corti (OC), the stereocilia on the apical surface of hair cells (HCs) are uniformly organized in a neural to abneural axis (or medial-laterally). This organization is regulated by planar cell polarity (PCP) signaling. Mutations of PCP genes, such as Vangl2, Dvl1/2, Celsr1, and Fzd3/6, affect the formation of HC orientation to varying degrees. Prickle1 is a PCP signaling gene that belongs to the prickle / espinas / testin family. Prickle1 protein is shown to be asymmetrically localized in the HCs of the OC, and this asymmetric localization is associated with loss of PCP in Smurf mutants, implying that Prickle1 is involved in HC PCP development in the OC. A follow-up study found no PCP polarity defects after loss of Prickle1 (Prickle1-/-) in the cochlea. We show here strong Prickle1 mRNA expression in the spiral ganglion by in situ hybridization and β-Gal staining, and weak expression in the OC by β-Gal staining. Consistent with this limited expression in the OC, cochlear HC PCP is unaffected in either Prickle1C251X/C251X mice or Prickle1f/f; Pax2-cre conditional null mice. Meanwhile, type II afferents of apical spiral ganglion neurons (SGN) innervating outer hair cells (OHC) have unusual neurite growth. In addition, afferents from the apex show unusual collaterals in the cochlear nuclei that overlap with basal turn afferents. Our findings argue against the role of Prickle1 in regulating hair cell polarity in the cochlea. Instead, Prickle1 regulates the polarity-related growth of distal and central processes of apical SGNs.