Early prosensory specification to develop competence in the otic epithelium is disrupted by mutations of Eya1, Pax2, Sox2, Jag1, and Gata3. Mutations in these genes apparently disrupt sensory competence and may affect Atoh1 upregulation, a gene known to be necessary for sensory cell differentiation within the ear. How these genes interact with each other and other factors within the genetic network of the ear to refine and restrict sensory specification and impart competence to the developing organ of Corti is not known. These genes also interact with other factors expressed adjacent to or within the developing organ of Corti and provide the context to allow prosensory cells, after cell cycle exit, to appropriately respond to Atoh1 expression and differentiate as hair cells. Gata3 is expressed throughout the early placode. As ear development continues Gata3 is restricted to all prosensory areas except that of the saccule. In addition, it is expressed in a subset of delaminating neuroblasts. Gata3 continues to be highly expressed in the cochlear sensory epithelia as cells differentiate, and is expressed in all cells of the organ of Corti through adult. The human disorder caused by haploinsufficiency of Gata3 is known as Hypoparathyriodism, Deafness, and Renal dysplasia syndrome, and has been linked in mice to early hair cell death. I investigated the role of Gata3 in cochlear neurosensory specification utilizing a mouse Gata3 knockout model and a conditionally deleted Gata3 line combined with two cre driver lines (Foxg1cre and Pax2cre). Although both cre lines are expressed in the inner ear with only a slight difference in onset of expression there are major phenotypic differences. While the Foxg1cre:Gata3f/f deletion resulted in an ear closely matching that of the null mutant with a cochlear duct devoid of neurosensory cells, the Pax2cre:Gata3f/f cochlear duct contained patches of partially differentiated hair cells. Through the use of qRT-PCR and in situ hybridization of both mutants I was able to paint a picture of how Gata3 interacts with other prosensory genes to upregulate downstream genes. In particular, Atoh1, was downregulated but not absent with the loss of Gata3. Indicating that Gata3 is one of a set of factors necessary for the proper upregulation of Atoh1 in the cochlea.

To coordinate visual perception and motor control in daily life where we are constantly surrounded by motion, we are dependent on normal visuomotor capacity. One essential prerequisite for normal visuomotor capacity is smooth pursuit eye movements (SP). Infants born very preterm (VPT = born <32 gestational weeks) are at high risk of developing disabilities in higher brain functions i.e. perception, cognition, concentration and coordination. In this thesis visuomotor capacity was investigated in a cohort of VPT infants (n = 113) and compared to control groups of full term (FT) infants. Levels of SP were measured at 2 and 4 months’ corrected age (CA). At 8 months’ CA reaching capacity toward a moving object was evaluated as this represents an executive activity guided by vision that develops at an early age. Lower levels of SP were found in the VPT infants compared to FT controls. The VPT boys showed higher levels of SP compared to the VPT girls. In VPT infants without major neonatal morbidities lower levels of SP was found compared to the FT controls. No difference in total capacity of gaze tracking was found, although the VPT infants lagged the object more at 4 months’ CA and used more saccades at 2 months’ CA. With age the VPT infants’ SP levels increased, but with a wider dispersion compared to the FT controls, and the levels of SP at 4 months’ CA corresponded to the levels of the FT infants at 2 months.  A number of perinatal risk factors were found to be negatively associated to lower levels of SP, and this effect was more pronounced in VPT infants with multiple risk factors,.  When evaluating the capacity to reach a moving object at 8 months’ CA, the VPT infants showed significantly more bimanual reach and more curved reaching paths to catch the object as compared to the FT control group. In conclusion, a delayed visuomotor capacity was found in VPT infants compared to FT control infants at 2, 4 and 8 months’ CA. Some VPT infants with perinatal risk factors did not develop in levels of SP between 2 and 4 months’ CA.