Expression of LHX3 and SOX2 during mouse inner ear development.

A cascade of transcription factors is believed to regulate the coordinate differentiation of primordial inner ear cells into the subtypes of hair cells and supporting cells. While candidate genes involved in this process have been identified, the temporal and spatial patterns of expression of many of these have not been carefully described during the extended period of inner ear development and functional maturation. We systematically examined the expression of two such transcription factors, LHX3 and SOX2, from the time of hair cell terminal mitoses into adulthood. We show that LHX3 is expressed specifically in auditory and vestibular hair cells soon after terminal mitoses and persists into the adult in vestibular hair cells. While SOX2 expression is widespread in the inner ear sensory epithelia prior to hair cell differentiation, it has a unique pattern of expression in the mature auditory and vestibular organs.

[1]  M. Thomasset,et al.  Calbindin (CaBP 28 kDa) localization in the peripheral vestibular system of various vertebrates , 1988, Hearing Research.

[2]  A. Griffith,et al.  Human nonsyndromic sensorineural deafness. , 2003, Annual review of genomics and human genetics.

[3]  N. Segil,et al.  p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti. , 1999, Development.

[4]  N. Segil,et al.  Math1-driven GFP expression in the developing nervous system of transgenic mice. , 2003, Gene expression patterns : GEP.

[5]  J. T. Corwin,et al.  Post-translational protein modification as the substrate for long-lasting memory , 2005 .

[6]  David J. Anderson,et al.  Neurogenin 1 Null Mutant Ears Develop Fewer, Morphologically Normal Hair Cells in Smaller Sensory Epithelia Devoid of Innervation , 2000, Journal of the Association for Research in Otolaryngology.

[7]  Mahendra Rao,et al.  SOX2, a Persistent Marker for Multipotential Neural Stem Cells Derived from Embryonic Stem Cells, the Embryo or the Adult , 2004, Developmental Neuroscience.

[8]  M. Kelley,et al.  From placode to polarization: new tunes in inner ear development , 2004, Development.

[9]  T. Hasson,et al.  Porcine myosin-VI: characterization of a new mammalian unconventional myosin , 1994, The Journal of cell biology.

[10]  D. Hilding,et al.  The development of the organ of Corti in the mouse. , 1965, Acta oto-laryngologica.

[11]  W. Gao,et al.  Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears , 2000, Nature Neuroscience.

[12]  D. Corey,et al.  Unconventional Myosins in Inner-Ear Sensory Epithelia , 1997, The Journal of cell biology.

[13]  H. Zoghbi,et al.  The role of Math1 in inner ear development: Uncoupling the establishment of the sensory primordium from hair cell fate determination. , 2002, Development.

[14]  T. Hasson Unconventional myosins, the basis for deafness in mouse and man. , 1997, American journal of human genetics.

[15]  R. Ruben Development of the inner ear of the mouse: a radioautographic study of terminal mitoses. , 1967, Acta oto-laryngologica.

[16]  Anna Lysakowski,et al.  Comparative morphology of rodent vestibular periphery. I. Saccular and utricular maculae. , 2005, Journal of neurophysiology.

[17]  Together at Last bHLH and LIM-HD Regulators Cooperate to Specify Motor Neurons , 2003, Neuron.

[18]  M. Montcouquiol,et al.  Math1 regulates development of the sensory epithelium in the mammalian cochlea , 2004, Nature Neuroscience.

[19]  S. Pfaff,et al.  LIM Homeodomain Factors Lhx3 and Lhx4 Assign Subtype Identities for Motor Neurons , 1998, Cell.

[20]  Ryosei Minoda,et al.  Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals , 2005, Nature Medicine.

[21]  A. Grüters,et al.  Molecular genetic defects in congenital hypothyroidism. , 2004, European journal of endocrinology.

[22]  S. Pfaff,et al.  Transcriptional codes and the control of neuronal identity. , 2002, Annual review of neuroscience.

[23]  A. Grüters,et al.  Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency , 2000, Nature Genetics.

[24]  S. Spicer,et al.  Ultrastructure indicative of ion transport in tectal, Deiters, and tunnel cells: differences between gerbil and chinchilla basal and apical cochlea. , 2003, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[25]  S. Rhodes,et al.  LIM-homeodomain genes in mammalian development and human disease , 2005, Molecular Biology Reports.

[26]  M. Wegner,et al.  From stem cells to neurons and glia: a Soxist's view of neural development , 2005, Trends in Neurosciences.

[27]  M. I. Lomax,et al.  Early Embryology of the Vertebrate Ear , 1998 .

[28]  G. Desmadryl,et al.  Development of calretinin immunoreactivity in the mouse inner ear , 1994, The Journal of comparative neurology.

[29]  J. Johnson,et al.  Progenitors of dorsal commissural interneurons are defined by MATH1 expression. , 1998, Development.

[30]  T. Hasson,et al.  Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells. , 1998, Development.

[31]  Bassem A. Hassan,et al.  Math1: an essential gene for the generation of inner ear hair cells. , 1999, Science.

[32]  A. Kiernan,et al.  The Notch Ligand JAG1 Is Required for Sensory Progenitor Development in the Mammalian Inner Ear , 2006, PLoS genetics.

[33]  F. Liu,et al.  A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development , 2006, Development.

[34]  Karen P. Steel,et al.  Sox2 is required for sensory organ development in the mammalian inner ear , 2005, Nature.

[35]  W. Brownell,et al.  Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems. , 2000, Genes & development.

[36]  Toshinori Hayashi,et al.  Expression of Prox1 during mouse cochlear development , 2006, The Journal of comparative neurology.

[37]  E. Huang,et al.  NeuroD-null mice are deaf due to a severe loss of the inner ear sensory neurons during development. , 2001, Development.

[38]  T. Hasson,et al.  Vertebrate Unconventional Myosins* , 1996, The Journal of Biological Chemistry.

[39]  Edwin W Rubel,et al.  Caspase Activation in Hair Cells of the Mouse Utricle Exposed to Neomycin , 2002, The Journal of Neuroscience.

[40]  G. Housley,et al.  Hair Cells – Beyond the Transducer , 2006, The Journal of Membrane Biology.

[41]  I. Varela-Nieto,et al.  Development of auditory and vestibular systems , 1983 .

[42]  Samuel L. Pfaff,et al.  Synchronization of Neurogenesis and Motor Neuron Specification by Direct Coupling of bHLH and Homeodomain Transcription Factors , 2003, Neuron.

[43]  Bernd Fritzsch,et al.  Proprioceptor Pathway Development Is Dependent on MATH1 , 2001, Neuron.

[44]  M. Thomasset,et al.  Calbindin (CaBP 28 kDa) appearance and distribution during development of the mouse inner ear. , 1988, Brain research.

[45]  R. Sidman,et al.  Serial section radioautography of the inner ear. Histological technique. , 1967, Archives of otolaryngology.

[46]  T. Jessell,et al.  Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes , 1994, Cell.

[47]  E. Rubel,et al.  Hair cell regeneration: winging our way towards a sound future , 2003, Current Opinion in Neurobiology.

[48]  A. Sher The embryonic and postnatal development of the inner ear of the mouse. , 1971, Acta oto-laryngologica. Supplementum.

[49]  R. Lovell-Badge,et al.  Multipotent cell lineages in early mouse development depend on SOX2 function. , 2003, Genes & development.

[50]  D. Lim,et al.  Developmental morphology of the mouse inner ear. A scanning electron microscopic observation. , 1985, Acta oto-laryngologica. Supplementum.

[51]  M. Wegner,et al.  Sox10 Is an Active Nucleocytoplasmic Shuttle Protein, and Shuttling Is Crucial for Sox10-Mediated Transactivation , 2002, Molecular and Cellular Biology.

[52]  K. Kawamoto,et al.  Math1 Gene Transfer Generates New Cochlear Hair Cells in Mature Guinea Pigs In Vivo , 2003, The Journal of Neuroscience.