GATA Factors Regulate Inner Ear Development and Midbrain Neurogenesis

................................................................................................................................7 Abbreviations........................................................................................................................8 1 Review of the literature .............................................................................................. 10 1.1 Functions of the ear ............................................................................................... 10 1.2 Inner ear structure ................................................................................................. 10 1.2.1 The vestibule and auditory compartments .......................................................... 10 1.2.2 Inner ear fluids .................................................................................................. 11 1.2.3 Sensory organs .................................................................................................. 11 1.2.4 Structure and function of hair cells .................................................................... 13 1.2.5 Supporting cells................................................................................................. 13 1.3 Inner ear development ........................................................................................... 14 1.3.1 Otic induction.................................................................................................... 14 1.3.1.1 Signaling molecules of FGF and WNT families ......................................... 14 1.3.2 Early morphogenesis – from placode to otic vesicle .......................................... 15 1.3.2.1 Patterning of the otic epithelium: intrinstic factors ..................................... 16 1.3.2.2 Patterning of the otic epithelium: hindbrain derived signals ....................... 16 1.3.3 Later morphogenesis: from otic vesicle to membranous labyrinth ...................... 17 1.3.3.1 Formation of the endolymphatic duct and sac ............................................ 17 1.3.3.2 Formation of the semicircular ducts ........................................................... 17 1.3.3.2.1 Molecular control of the epithelial pouches outgrowth ......................... 18 1.3.3.2.2 Regulation of the fusion plate formation and clearance ......................... 19 1.3.3.2.3 Continued growth of semicircular ducts ............................................... 19 1.3.3.3 Regulation of cochlear morphogenesis ....................................................... 19 1.3.4 Sensorineural determination and differentiation ................................................. 20 1.3.4.1 Development of the vestibulocochlear ganglion ......................................... 21 1.3.4.1.1 Regulation of neuronal fate by proneural genes and NOTCH signaling 21 1.3.4.2 Sensory determination ............................................................................... 22 1.3.4.3 Specification and development of distinct sensory organs .......................... 23 1.3.4.4 Cell fate determination in sensory organs ................................................... 23 1.3.4.5 Differentiation of hair cells ........................................................................ 24 1.4 Sensorineural hearing disorders and regeneration of sensory hair cells .................. 25 1.4.1 Molecular background of sensorineural deafness in humans and domestic animals 25 1.4.2 Induction of hair cell regeneration – restoring hearing loss? .............................. 26 1.5 Development and structure of the midbrain ........................................................... 27 1.5.1 Anteroposterior patterning of the midbrain ........................................................ 28 1.5.2 Dorsoventral patterning of the midbrain ............................................................ 29 1.5.3 Neuronal cell types in midbrain ......................................................................... 29 1.5.3.1 Determination and specification of glutamatergic and GABAergic neurons 30 1.6 GATA transcription factors in development .......................................................... 30 1.6.1 GATA2 and GATA3 in embryonic development ............................................... 31 1.6.2 GATA2 and GATA3 in inner ear ...................................................................... 33 1.6.3 GATA2 and GATA3 in nervous system ............................................................ 34