Formation of the mouse cochlea: roles of Sonic hedgehog
Abstract
The formation of the mammalian cochlea is dependent on signalling from its surrounding tissues during embryogenesis. Using genetically engineered mutant mice and surgically manipulated chicken embryos, we demonstrated that Sonic hedgehog (Shh) secreted from the developing notochord and the floor plate is important for specification of ventral inner-ear structures that include the cochlear duct. Additionally, tissue-specific knockout of Shh in the developing spiral ganglion indicates that this source of Shh is required for mediating growth of the cochlear duct, timing of terminal mitosis of hair cell precursors, and subsequent differentiation of nascent hair cells along the cochlear duct.References
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Bok, J., Dolson, D.K., Hill, P., Ruther, U., Epstein, D.J., and Wu, D.K. (2007). “Opposing gradients of Gli repressor and activators mediate Shh signaling along the dorsoventral axis of the inner ear,” Development, 134, 1713-1722.
Bok, J., Raft, S., Kong, K.A., Koo, S.K., Drager, U.C., and Wu, D.K. (2011). “Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear,” Proc. Natl. Acad. Sci. USA, 108, 161-166.
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Borycki, A., Brown, A.M., and Emerson, C.P., Jr. (2000). “Shh and Wnt signaling pathways converge to control Gli gene activation in avian somites,” Development, 127, 2075-2087.
Bose, J., Grotewold, L., and Ruther, U. (2002). “Pallister-Hall syndrome phenotype in mice mutant for Gli3,” Hum. Mol. Genet., 11, 1129-1135.
Braunstein, E.M., Crenshaw Iii, E.B., Morrow, B.E., and Adams, J.C. (2008). “Cooperative function of Tbx1 and Brn4 in the periotic mesenchyme is necessary for cochlea formation,” J. Assoc. Res. Otolaryngol., 9, 33-43.
Brown, A.S., and Epstein, D.J. (2011). “Otic ablation of smoothened reveals direct and indirect requirements for Hedgehog signaling in inner ear development,” Development, 138, 3967-3976.
Chang, W., Cole, L.K., Cantos, R., and Wu, D.K. (2003). “Molecular genetics of vestibular organ development,” in Springer Handbook of Auditory Research: The vestibular system, Vol. 19. Edited by S.M. Highstein, R.F. Fay, and A.N. Popper (New York: Springer-Verlag).
Driver, E.C., Pryor, S.P., Hill, P., Turner, J., Ruther, U., Biesecker, L.G., Griffith, A.J., and Kelley, M.W. (2008). “Hedgehog signaling regulates sensory cell formation and auditory function in mice and humans,” J. Neurosci., 28, 7350-7358.
Hayashi, S., and McMahon, A.P. (2002). “Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse,” Dev. Biol., 244, 305-318.
Hebert, J.M., and McConnell, S.K. (2000). “Targeting of cre to the Foxg1 (BF-1) locus mediates loxP recombination in the telencephalon and other developing head structures,” Dev. Biol., 222, 296-306.
Ingham, P.W., and McMahon, A.P. (2001). “Hedgehog signaling in animal development: paradigms and principles,” Genes Dev., 15, 3059-3087.
Kang, S., Graham, J.M., Jr., Olney, A.H., and Biesecker, L.G. (1997). “GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome,” Nat. Genet., 15, 266-268.
Koundakjian, E.J., Appler, J.L., and Goodrich, L.V. (2007). “Auditory neurons make stereotyped wiring decisions before maturation of their targets,” J. Neurosci., 27, 14078-14088.
Lee, Y.S., Liu, F., and Segil, N. (2006). “A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development,” Development, 133, 2817-2826.
Li, C.W., Van De Water, T.R., and Ruben, R.J. (1978). “The fate mapping of the eleventh and twelfth day mouse otocyst: an in vitro study of the sites of origin of the embryonic inner ear sensory structures,” J. Morphol., 157, 249-267.
Liang, J.K., Bok, J., and Wu, D.K. (2010). “Distinct contributions from the hindbrain and mesenchyme to inner ear morphogenesis,” Dev. Biol., 337, 324-334.
Litingtung, Y., Dahn, R.D., Li, Y., Fallon, J.F., and Chiang, C. (2002). “Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity,” Nature, 418, 979-983.
Liu, Z., Owen, T., Zhang, L., and Zuo, J. (2010). “Dynamic expression pattern of Sonic hedgehog in developing cochlear spiral ganglion neurons,” Dev. Dyn. 239, 1674-1683.
Morsli, H., Choo, D., Ryan, A., Johnson, R., and Wu, D.K. (1998). “Development of the mouse inner ear and origin of its sensory organs,” J. Neurosci., 18, 3327-3335.
Phippard, D., Lu, L., Lee, D., Saunders, J.C., and Crenshaw, E.B., 3rd (1999). “Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear,” J. Neurosci., 19, 5980-5989.
Quinones, H.I., Savage, T.K., Battiste, J., and Johnson, J.E. (2010). “Neurogenin 1 (Neurog1) expression in the ventral neural tube is mediated by a distinct enhancer and preferentially marks ventral interneuron lineages,” Dev. Biol., 340, 283-292.
Raft, S., Koundakjian, E.J., Quinones, H., Jayasena, C.S., Goodrich, L.V., Johnson, J.E., Segil, N., and Groves, A.K. (2007) “Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development,” Development, 134, 4405-4415.
Riccomagno, M.M., Martinu, L., Mulheisen, M., Wu, D.K., and Epstein, D.J. (2002). “Specification of the mammalian cochlea is dependent on Sonic hedgehog,” Genes Dev., 16, 2365-2378.
Riccomagno, M.M., Takada, S., and Epstein, D.J. (2005). “Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh,” Genes Dev., 19, 1612-1623.
Ruben, R.J. (1967). “Development of the inner ear of the mouse: a radioautographic study of terminal mitoses,” Acta Otolaryngol. Suppl., 220, 1-44.
Swanson, G.J., Howard, M., and Lewis, J. (1990). “Epithelial autonomy in the development of the inner ear of a bird embryo,” Dev. Biol., 137, 243-257.
Tateya, T., Imayoshi, I., Tateya, I., Hamaguchi, K., Torii, H., Ito, J., and Kageyama, R. (2013). “Hedgehog signaling regulates prosensory cell properties during the basal-to-apical wave of hair cell differentiation in the mammalian cochlea,” Development, 140, 3848-3857.
te Welscher, P., Zuniga, A., Kuijper, S., Drenth, T., Goedemans, H.J., Meijlink, F., and Zeller, R. (2002). “Progression of vertebrate limb development through SHH-mediated counteraction of GLI3,” Science, 298, 827-830.
Wu, D.K., and Kelley, M.W. (2012). “Molecular mechanisms of inner ear development,” Cold Spring Harb. Perspect. Biol., 4, a008409.
Bok, J., Dolson, D.K., Hill, P., Ruther, U., Epstein, D.J., and Wu, D.K. (2007). “Opposing gradients of Gli repressor and activators mediate Shh signaling along the dorsoventral axis of the inner ear,” Development, 134, 1713-1722.
Bok, J., Raft, S., Kong, K.A., Koo, S.K., Drager, U.C., and Wu, D.K. (2011). “Transient retinoic acid signaling confers anterior-posterior polarity to the inner ear,” Proc. Natl. Acad. Sci. USA, 108, 161-166.
Bok, J., Zenczak, C., Hwang, C.H., and Wu, D. K. (2013). “Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells,” Proc. Natl. Acad. Sci. USA, 110, 13869-13874.
Borycki, A., Brown, A.M., and Emerson, C.P., Jr. (2000). “Shh and Wnt signaling pathways converge to control Gli gene activation in avian somites,” Development, 127, 2075-2087.
Bose, J., Grotewold, L., and Ruther, U. (2002). “Pallister-Hall syndrome phenotype in mice mutant for Gli3,” Hum. Mol. Genet., 11, 1129-1135.
Braunstein, E.M., Crenshaw Iii, E.B., Morrow, B.E., and Adams, J.C. (2008). “Cooperative function of Tbx1 and Brn4 in the periotic mesenchyme is necessary for cochlea formation,” J. Assoc. Res. Otolaryngol., 9, 33-43.
Brown, A.S., and Epstein, D.J. (2011). “Otic ablation of smoothened reveals direct and indirect requirements for Hedgehog signaling in inner ear development,” Development, 138, 3967-3976.
Chang, W., Cole, L.K., Cantos, R., and Wu, D.K. (2003). “Molecular genetics of vestibular organ development,” in Springer Handbook of Auditory Research: The vestibular system, Vol. 19. Edited by S.M. Highstein, R.F. Fay, and A.N. Popper (New York: Springer-Verlag).
Driver, E.C., Pryor, S.P., Hill, P., Turner, J., Ruther, U., Biesecker, L.G., Griffith, A.J., and Kelley, M.W. (2008). “Hedgehog signaling regulates sensory cell formation and auditory function in mice and humans,” J. Neurosci., 28, 7350-7358.
Hayashi, S., and McMahon, A.P. (2002). “Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse,” Dev. Biol., 244, 305-318.
Hebert, J.M., and McConnell, S.K. (2000). “Targeting of cre to the Foxg1 (BF-1) locus mediates loxP recombination in the telencephalon and other developing head structures,” Dev. Biol., 222, 296-306.
Ingham, P.W., and McMahon, A.P. (2001). “Hedgehog signaling in animal development: paradigms and principles,” Genes Dev., 15, 3059-3087.
Kang, S., Graham, J.M., Jr., Olney, A.H., and Biesecker, L.G. (1997). “GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome,” Nat. Genet., 15, 266-268.
Koundakjian, E.J., Appler, J.L., and Goodrich, L.V. (2007). “Auditory neurons make stereotyped wiring decisions before maturation of their targets,” J. Neurosci., 27, 14078-14088.
Lee, Y.S., Liu, F., and Segil, N. (2006). “A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development,” Development, 133, 2817-2826.
Li, C.W., Van De Water, T.R., and Ruben, R.J. (1978). “The fate mapping of the eleventh and twelfth day mouse otocyst: an in vitro study of the sites of origin of the embryonic inner ear sensory structures,” J. Morphol., 157, 249-267.
Liang, J.K., Bok, J., and Wu, D.K. (2010). “Distinct contributions from the hindbrain and mesenchyme to inner ear morphogenesis,” Dev. Biol., 337, 324-334.
Litingtung, Y., Dahn, R.D., Li, Y., Fallon, J.F., and Chiang, C. (2002). “Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity,” Nature, 418, 979-983.
Liu, Z., Owen, T., Zhang, L., and Zuo, J. (2010). “Dynamic expression pattern of Sonic hedgehog in developing cochlear spiral ganglion neurons,” Dev. Dyn. 239, 1674-1683.
Morsli, H., Choo, D., Ryan, A., Johnson, R., and Wu, D.K. (1998). “Development of the mouse inner ear and origin of its sensory organs,” J. Neurosci., 18, 3327-3335.
Phippard, D., Lu, L., Lee, D., Saunders, J.C., and Crenshaw, E.B., 3rd (1999). “Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear,” J. Neurosci., 19, 5980-5989.
Quinones, H.I., Savage, T.K., Battiste, J., and Johnson, J.E. (2010). “Neurogenin 1 (Neurog1) expression in the ventral neural tube is mediated by a distinct enhancer and preferentially marks ventral interneuron lineages,” Dev. Biol., 340, 283-292.
Raft, S., Koundakjian, E.J., Quinones, H., Jayasena, C.S., Goodrich, L.V., Johnson, J.E., Segil, N., and Groves, A.K. (2007) “Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development,” Development, 134, 4405-4415.
Riccomagno, M.M., Martinu, L., Mulheisen, M., Wu, D.K., and Epstein, D.J. (2002). “Specification of the mammalian cochlea is dependent on Sonic hedgehog,” Genes Dev., 16, 2365-2378.
Riccomagno, M.M., Takada, S., and Epstein, D.J. (2005). “Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh,” Genes Dev., 19, 1612-1623.
Ruben, R.J. (1967). “Development of the inner ear of the mouse: a radioautographic study of terminal mitoses,” Acta Otolaryngol. Suppl., 220, 1-44.
Swanson, G.J., Howard, M., and Lewis, J. (1990). “Epithelial autonomy in the development of the inner ear of a bird embryo,” Dev. Biol., 137, 243-257.
Tateya, T., Imayoshi, I., Tateya, I., Hamaguchi, K., Torii, H., Ito, J., and Kageyama, R. (2013). “Hedgehog signaling regulates prosensory cell properties during the basal-to-apical wave of hair cell differentiation in the mammalian cochlea,” Development, 140, 3848-3857.
te Welscher, P., Zuniga, A., Kuijper, S., Drenth, T., Goedemans, H.J., Meijlink, F., and Zeller, R. (2002). “Progression of vertebrate limb development through SHH-mediated counteraction of GLI3,” Science, 298, 827-830.
Wu, D.K., and Kelley, M.W. (2012). “Molecular mechanisms of inner ear development,” Cold Spring Harb. Perspect. Biol., 4, a008409.
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Published
2015-12-15
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Bok, J., Zenczak, C., Hwang, C., & Wu, D. K. (2015). Formation of the mouse cochlea: roles of Sonic hedgehog. Proceedings of the International Symposium on Auditory and Audiological Research, 4, 77–88. Retrieved from https://proceedings.isaar.eu/index.php/isaarproc/article/view/2013-09
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2013/2. Physiological correlates and modeling of auditory plasticity
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