Although the role of retinoic acid (RA) signalling in odontogenesis is well established, its involvement in the repair of injured tooth germs remains unclear. To investigate this, we generated a Tg(scpp5:Dendra2-NTR) zebrafish line for labelling tooth germ cells and established a tooth germ injury model using the nitroreductase (NTR)/metronidazole (MTZ) system. We then modulated RA signalling by exogenous activation with RA, retinol, retinal, talarozole (TZ) or Tg(hsp70l:aldh1a2-p2a-mCherry; cryaa:venus), and by suppression with 4-diethylaminobenzaldehyde (DEAB) or Tg(hsp70l:dnRARAA-p2a-DsRed; cryaa:venus), to examine its function in tooth germ repair. Following targeted ablation of tooth germ cells, RA signalling was activated, with aldh1a2 showing the most pronounced upregulation. Exogenous RA promoted injury-induced tooth germ repair, whereas its precursors (retinol and retinal) had no significant effect on aldh1a2 expression or repair. Pharmacological inhibition of RA degradation with TZ enhanced repair, while dominant-negative inhibition of RA signalling impaired it. Furthermore, modulation of aldh1a2 revealed its essential role: inhibition with DEAB attenuated repair, whereas genetic activation facilitated tissue restoration. In summary, this study clarifies the regulatory role of RA signalling in tooth germ injury repair, offering a theoretical foundation and potential therapeutic targets for the treatment of injured tooth germs.
Liu et al. (Mon,) studied this question.