Engrailed1 in Parvalbumin‐Positive Neurons Regulates Eye‐Specific Retinogeniculate Segregation and Visual Function

Homeobox transcription factor Engrailed1 (En1) is expressed in the ectoderm and mediates the establishment of retinotectal topography, but its role in eye-specific retinogeniculate segregation and visual function remains unclear. Parvalbumin (PV) neurons, which are widely distributed in the visual pathway, play a crucial role in visual development and function. In this study, we conditionally knocked out En1 gene in PV neurons and found an expansion of the ipsilateral eye projection, while no significant effects were observed in the contralateral eye projection. Additionally, we observed a decrease in the number of PV neurons in PV-Cre:En1^fl/fl mice, accompanied by an increased level of cleaved caspase-3 in PV neurons. Furthermore, the genetic ablation of PV neurons in the retina through intraocular AAV-DIO-Caspase3 injection in PV-Cre mice was sufficient to disrupt retinogeniculate segregation. Finally, we observed that PV-Cre:En1^fl/fl mice exhibited enhanced visual depth perception in the visual cliff test. These results demonstrate that En1 in PV neurons participates in eye-specific retinogeniculate segregation through cell survival and regulates binocular vision.