Spatiotemporal distribution of a signal driving spinal cord regeneration in the axolotl

TANAKA, ELLY M; RODRIGO-ALBORS AIDA; CURA COSTA, EMANUEL; CHARA, OSVALDO

Conferencia; Latin American Society for Developmental Biology (LASDB) meeting 2019; 2019

Unlike mammals, the axolotl is able to regenerate the spinal cord after tail amputation. We previously found that this process leads to the reactivation of developmental-like programs in spinal cord ependymal cells, accelerating cell proliferation while transiently interrupting neurogenesis (Rodrigo Albors et al., 2015, 4:e10230. doi: 10.7554/eLife.10230). We also determined a high-proliferation zone that initiates 4 days after amputation within the 800 μm anterior to the tip of the regenerating spinal cord and demonstrated that the acceleration of the cell cycle is the major driver of regenerative outgrowth (Rost et al., 2016, 5. pii: e20357. doi: 10.7554/eLife.20357). What are the mechanisms responsible for this spatiotemporal pattern of cell proliferation, however, are not yet known. By following a modelling approach tightly supported by previous experimental data, we show that the proliferative spatiotemporal pattern in the regenerating axolotl spinal cord is consistent with a signal that starts recruiting ependymal cells within two days after the injury and spreads about one millimeter from the amputation plane. Our model shows that while G1, G2 and M phases play a minor role, shortening of S phase in the ependymal cells is the major driver of regenerative spinal cord outgrowth in axolotls.