Fu, Tianyue. Tafa3 is required for the development of photoreceptor outer segment and horizontal cell process in the retina. Retrieved from https://doi.org/doi:10.7282/t3-dbam-jj55
DescriptionRetinal development is a very complicated process including neural circuit formation. Various retinal cells are required to correctly connect to each other at a specific time point and location for successful visual signal transduction. Photoreceptor cells in the retina, including rods and cones, play an essential role in detecting and forming the visual signal. Specifically, the outer segment (OS) of the photoreceptor cells detects the visual signal and transforms it into electrical signal. The electrical signal propagates to synapses of various interneurons and retinal ganglion cells and reaches the visual cortex in the brain. However, the molecular mechanisms that govern the development of photoreceptor OS and horizontal cell (HC) process have not been fully elucidated. In search for genes important for retinal development, the Cai lab identified a TAFA chemokine like family member 3 (Tafa3) in the developing mouse retina through bioinformatic analysis on single-cell RNA-seq datasets. Studies have established Tafa3 expression in the mouse brain and eye and is known to function in axonal sprouting after brain injury. The lack of Tafa3 in the brain leads to immune dysregulation of autism spectrum disorders along with defects in synaptic transmission suggesting the clinical importance of Tafa3. This study is to characterize the function of Tafa3 in the HC process and photoreceptor cell OS development. Tafa3 has high expression in the peak developmental stages of OS and HC process by immunohistochemical analysis, indicating its function in these biological processes. The specific Tafa3 function in the OS development and HC process in vivo was investigated via short hairpin RNA (shRNA)-mediated gene knockdown approach via subretinal injection, electroporation, and RT-PCR techniques. Tafa3 knockdown causes aberrant axonal growth of interneurons and disorganized photoreceptor OS, along with the changes in expression of genes associated with rod terminal synaptic connection, and OS development. These results provide new insight into Tafa3 mediated retinal development.