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Vladimir Muzyka, Tudor C Badea; Pou4f1/Brn3a regulates neurite- and synapse-associated genes during Retinal Ganglion Cell development. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2595.
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© ARVO (1962-2015); The Authors (2016-present)
The Pou4f/Brn3 family of POU-domain transcription factors regulates the development of the majority of retinal ganglion cells (RGCs). Brn3a, one of the three family members, is expressed in a subset of RGCs, and is required for the development of specific RGC types, with dense, small area dendritic arbors. Loss of Brn3a also affects the morphology of other RGC subtypes. Currently, it is not clear what molecular mechanisms and genes are responsible for the specification of those cells during development, and how Brn3a regulates it.
Our group has previously performed a large-scale RNA sequencing screen for molecules (Sajgo, Ghinia and Badea, unpublished) regulated by Brn3-s in RGCs at postnatal day 3. We now use RT-PCR, in situ hybridization and protein immuno-detection in Brn3aKO retinas and controls in order to validate several of the potential targets and describe their expression profile during postnatal RGC development.
We describe the expression profiles of 28 potential Brn3a-RGC target genes at several postnatal ages, beginning with P0 (postnatal day 0) and into the adult age. The genes comprise transcription factors, posttranscriptional regulators, enzymes, trafficking, signaling and adhesion molecules. We find that, whereas most of the identified targets exhibit RGC specificity and/or Brn3a dependency at the screening target age (P3), many of them change their expression profile dynamically, and only a fraction preserve RGC specificity throughout postnatal development into adulthood.
The Pou4f1/Brn3a dependent RGC transcriptional program consists of at least 20 genes and/or transcripts. Some of these are RGC specific, while others are dynamically expressed in RGCs and/or other retinal cell types at different developmental stages. Based on conserved domain structure and previously published evidence many of the identified molecules could be involved in dendrite morphology formation and synaptogenesis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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