Quantification of cell behaviours in the regenerating spinal cord

DEUTSCH, ANDREAS; RODRIGO-ALBORS AIDA; TANAKA, ELLY M.; MAZUROV, VLADIMIR; CHARA, OSVALDO; BRUSCH, LUTZ; ROST, FABIAN

Heidelberg

Conferencia; Quantitative Principles in Biology; 2017

EMBO

QuestionRegeneration, theability to recreate lost tissues is a long studied question inbiology. Strikingly, mammals have generally poor regenerativeabilities. On the contrary, the Mexican salamander or axolotl isuniquely able to mobilize neural stem cells to completely regeneratemany lost neural tissues including the spinal cord. An outstandingbiological question is why this animal can and why so many otherspecies, including mammals, can?t. To answer this question we firstneed to understand what the cellular mechanisms controlling axolotlspinal cord regeneration are.After tailamputation the spinal cord regrows about 2 mm within 1 week. What arethe cell scale mechanisms that drive this tissue outgrowth? Methods & ResultsMorphogeneticprocesses like cell proliferation, and (de-)differentiation, cellularrearrangements are obvious candidates. We aimed to quantify them bytightly linking quantitative data analysis and mathematicalmodelling. We quantified thedensity of neural stem cells and mitotic events along theanteroposterior axis in the axolotl spinal cord during the first weekof regeneration. We analyzed these data with an empiricalmathematical model of two spatial zones of cell proliferation alongthe anteroposterior axis using Bayesian inference. This analysisindicated a region close to the amputation plane that shows anincrease in cell proliferation. To estimate the proliferation ratedynamics, we quantified and modelled the incorporation of a thymidineanalog (BrdU) in the regenerating spinal cord. Furthermore, wetracked individual cell clones to estimate the rate of celldisplacements and hence the flux of cells into the regenerating zone.Finally, we setup a mechanistic mathematical model of spinal cord outgrowth duringregeneration that incorporates proliferation, differentiation andcell displacements. By comparing this model to spinal cord outgrowthdata we can show that the proliferation in a zone close to theamputation plane is the key to explain the observed outgrowth.h2 { margin-top: 0.03in; margin-bottom: 0in; direction: ltr; color: rgb(46, 116, 181); text-align: left; page-break-inside: avoid; }h2.western { font-family: "Calibri Light", serif; font-size: 13pt; font-weight: normal; }h2.cjk { font-family: "Droid Sans Fallback"; font-size: 13pt; font-weight: normal; }h2.ctl { font-size: 13pt; font-weight: normal; }p { margin-bottom: 0.1in; direction: ltr; line-height: 120%; text-align: left; }a:link { }