A KNOCK-IN <EM>IGFN1</EM><SUP>ICRE</SUP> TRANSGENIC LINE PROVIDES PARTIAL DEVELOPMENTAL ACCESS TO DIRECTION SELECTIVE TYPE-7 BIPOLAR CELLS

Visual information processing in the vertebrate retina emerges gradually through coordinated developmental events, yet the timeline by which bipolar cells acquire selectivity to visual features remains unclear. A major barrier is the limited genetic access to bipolar subtypes during early postnatal stages, before and around the time they become light responsive. Recent comprehensive single-cell transcriptomic and bipolar cell birthdating studies suggests a path forward by highlighting Igfn1 as a molecular marker for type-7 bipolar cells (BC7), a subtype that exhibits direction-selective responses in adult.
Here, we generated an Igfn1^iCre knock-in mouse line and characterized Igfn1 positive cell morphology from birth to adult using Cre-dependent tdTomato reporter and viral labeling. We found Igfn1-positive cells first appeared in the outer retina at postnatal day 4 (P4), and later into the inner nuclear layer by P12–P15, predominantly labeling bipolar cells and some amacrine populations. At P15, about 71% of labeled bipolar cells stratified their axons in the S4 sublamina of the inner plexiform layer, consistent with documented BC7 morphology. In the adult retina, the widespread Igfn1-labeling appears slightly dominated in amacrine cells. Finally, to validate these observations, we examined Igfn1 expression in the publicly available Mouse Retina Cell Atlas. This analysis confirmed strong Igfn1 enrichment in BC7 and revealed lower-level expression in additional bipolar subtypes and amacrine cluster, mirroring experimental results.
Overall, these results reveal Igfn1^iCre as a potential developmental tool for BC7 access and reveal unexpected, dynamic Igfn1 expression across retina maturation period.