| First Author | Duan LJ | Year | 2023 |
| Journal | Biol Open | Volume | 12 |
| Issue | 1 | PubMed ID | 36625299 |
| Mgi Jnum | J:339542 | Mgi Id | MGI:7429245 |
| Doi | 10.1242/bio.059684 | Citation | Duan LJ, et al. (2023) Tailless and hypoxia inducible factor-2alpha cooperate to sustain proangiogenic states of retinal astrocytes in neonatal mice. Biol Open 12(1) |
| abstractText | Tailless (TLX, an orphan nuclear receptor) and hypoxia inducible factor-2alpha (HIF2alpha) are both essential for retinal astrocyte and vascular development. Tlx-/- mutation and astrocyte specific Hif2alpha disruption in Hif2alphaf/f/GFAPCre mice are known to cause defective astrocyte development and block vascular development in neonatal retinas. Here we report that TLX and HIF2alpha support retinal angiogenesis by cooperatively maintaining retinal astrocytes in their proangiogenic states. While Tlx+/- and Hif2alphaf/+/GFAPCre mice are phenotypically normal, Tlx+/-/Hif2alphaf/+/GFAPCre mice display precocious retinal astrocyte differentiation towards non-angiogenic states, along with significantly reduced retinal angiogenesis. In wild-type mice, TLX and HIF2alpha coexist in the same protein complex, suggesting a cooperative function under physiological conditions. Furthermore, astrocyte specific disruption of Phd2 (prolyl hydroxylase domain protein 2), a manipulation previously shown to cause HIF2alpha accumulation, did not rescue retinal angiogenesis in Tlx-/- background, which suggests functional dependence of HIF2alpha on TLX. Finally, the expression of fibronectin and VEGF-A is significantly reduced in retinal astrocytes of neonatal Tlx+/-/Hif2alphaf/+/GFAPCre mice. Overall, these data indicate that TLX and HIF2alpha cooperatively support retinal angiogenesis by maintaining angiogenic potential of retinal astrocytes. |
