a) Development of Brn3a dependent RGC types. This year we have focused on several downstream targets of the transcription factor Brn3a, and have performed a more in depth characterization of their cellular and subcellular localization, and generated and/or employed combinatorial genetics to characterize their expression and function in RGC subtypes. In collaboration with Chai-An Mao at UT Health Science Center, we have defined the genetic interactions between Brn3a and Tbr1 in the development of specific RGC subtypes. Taking advantage of our previously published work on the partial expression overlap between Brn3a and the neurotrophin receptor Ret, we have uncovered a genetic interaction between the Neurotrophin receptor and the transcription factor, that results in a competitive mechanism between distinct RGC types during development. Manuscript is in preparation. In addition we are generating genetic tools for two further novel or recently described RGC markers that appear to be regulated by Brn3a. b) We have nearly completed our characterization of our novel Dre-dependent Brn3c-Cre conditional knock-out (manuscript in preparation) and are using our Brn3 genetic reporters to characterize further RGC subtypes, in collaboration with expert physiology and circuit groups. c) We have completed our survey of Copine expression in retina cell types, and find a high degree of expression overlap between Copines 5, 6 and 9 in Amacrines and RGCs, while Copine 4 seems to be more selective for RGCs. We are addressing the biochemical and cell biological function of these genes using yeast two hybrid, pull-down mass spectrometry and gain and loss of function paradigms in vivo and in vitro (One paper published, one in preparation). d) We have implemented a newly develop spike sorting algorithm, in collaboration with computational biologists, and have carried out a large scale survey of RGC defects in Brn3b KO retinas (manuscript in preparation). e) We have completed an in depth analysis of visually evoked defense responses in global or retina specific Brn3b KO mice, and find suprprisngly specific defects in these animals (Manuscript is under review). f) We have followed up our collaboration on RGC-32 and generated a RGC-32 conditional mouse that will allow us to tease apart the cellular role of this cell cycle regulator in tissue remodeling, and experimental models of neuronal inflammatory diseases.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Ghahari, Alireza; Kumar, Sumit R; Badea, Tudor C (2018) Identification of Retinal Ganglion Cell Firing Patterns Using Clustering Analysis Supplied with Failure Diagnosis. Int J Neural Syst 28:1850008
Tatomir, Alexandru; Tegla, Cosmin A; Martin, Alvaro et al. (2018) RGC-32 regulates reactive astrocytosis and extracellular matrix deposition in experimental autoimmune encephalomyelitis. Immunol Res :
Parmhans, Nadia; Sajgo, Szilard; Niu, Jingwen et al. (2018) Characterization of retinal ganglion cell, horizontal cell, and amacrine cell types expressing the neurotrophic receptor tyrosine kinase Ret. J Comp Neurol 526:742-766
Muzyka, Vladimir Vladimirovich; Brooks, Matthew; Badea, Tudor Constantin (2018) Postnatal developmental dynamics of cell type specification genes in Brn3a/Pou4f1 Retinal Ganglion Cells. Neural Dev 13:15
Rus, Violeta; Nguyen, Vinh; Tatomir, Alexandru et al. (2017) RGC-32 Promotes Th17 Cell Differentiation and Enhances Experimental Autoimmune Encephalomyelitis. J Immunol 198:3869-3877
Somasundaram, Preethi; Wyrick, Glenn R; Fernandez, Diego Carlos et al. (2017) C-terminal phosphorylation regulates the kinetics of a subset of melanopsin-mediated behaviors in mice. Proc Natl Acad Sci U S A 114:2741-2746
Kretschmer, Friedrich; Tariq, Momina; Chatila, Walid et al. (2017) Comparison of optomotor and optokinetic reflexes in mice. J Neurophysiol 118:300-316
Sajgo, Szilard; Ghinia, Miruna Georgiana; Brooks, Matthew et al. (2017) Molecular codes for cell type specification in Brn3 retinal ganglion cells. Proc Natl Acad Sci U S A 114:E3974-E3983
Wang, Xu; Zhao, Lian; Zhang, Yikui et al. (2017) Tamoxifen Provides Structural and Functional Rescue in Murine Models of Photoreceptor Degeneration. J Neurosci 37:3294-3310
Wang, Xu; Zhao, Lian; Zhang, Jun et al. (2016) Requirement for Microglia for the Maintenance of Synaptic Function and Integrity in the Mature Retina. J Neurosci 36:2827-42

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