Tbx genes influence early gene expression and photoreceptor patterning in the chick retina

Abstract

The retina, our sensory organ for vision, displays distinct photoreceptor distributions and can have a specialized region for high visual acuity. The establishment of these spatial patterns during development depends on regionally restricted transcription factors and signaling molecules. Members of the T-box family of transcription factors, Tbx2, Tbx3, and Tbx5, show such restricted patterns of expression, with a dorsal high to ventral low pattern in the early retina. Their potential regulatory interactions and roles in patterning have not been fully explored. Here, we investigated their regulatory interactions by overexpression (OE) and knockdown (KD) approaches. We found that Tbx2, Tbx3, and Tbx5, directly or indirectly regulate each other as well as other early, patterned genes, including Fgf8, Cyp26a1, Cyp26c1, Cyp1b1, Raldh1, Ventroptin, and Bmp2. KD of any one of these Tbx genes increased rod photoreceptor density in a specific region of the retina, whereas Tbx2 loss additionally reduced the number of UV cones throughout the retina. Notably, KD of Tbx2, Tbx3, or Tbx5 consistently resulted in a smaller rod-free zone (RFZ), a domain within the high acuity area. These findings demonstrate that T-box transcription factors form a coordinated regulatory network that governs regional gene expression and photoreceptor patterning. HighlightsO_LITbx2, Tbx3, and Tbx5 regulate each other during chick retinal development C_LIO_LITbx2, Tbx3, and Tbx5 regulate the expression of early patterned genes, including Fg8, Cyp26c1, Cyp26a1, Cyp1b1, and Bmp2 C_LIO_LIKnockdown of either Tbx2/3/5 increased rod numbers in the equatorial retina and reduced the size of the rod-free zone (RFZ) C_LIO_LITbx2 knockdown decreased UV cone numbers dorsally, ventrally and in the RFZ C_LIO_LITbx2, Tbx3, and Tbx5 had no impact on green or red cone abundance C_LI