Spinal neurogenesis:From modeling to experimentation

We showed that neural progenitors are widely heterogeneous with respect to cell cycle length with the G1 phase contributing the most to this variability. In addition, the CDC25B phosphatase known to regulate the G2/M transition indirectly increases the duration of the G1 phase, partly through delaying passage through the restriction point. We propose that CDC25B increases the heterogeneity of G1 phase length, revealing a previously undescribed mechanism of G1 lengthening that is associated with tissue development (Molina et al., 2022).

We have shown that, in the spinal cord, CDC25B stimulates neurogenic mode of divisions (Bonnet et al., 2018). In this tissue, three modes of division have been described: proliferative division, which generates two progenitors; asymmetric neurogenic division, which yields one progenitor and one neuron; and terminal neurogenic division, which produces two neurons. During development, the patterns of progenitor cell divisions shift from proliferative to differentiative divisions to generate the appropriate number of neurons to build functional neural circuits (Saade et al., 2012).  We have developed mathematical models and found two that are compatible with the evolution of spinal neurogenesis at the population levels (Azaïs et al., 2019). We are now refining these models to analyze them at the cell scale. We have generated tree of descend using the models and showed that both models give different outputs.  We are now generating experimental trees of descent to be able to discriminate which mathematical model recapitulate the best experimental results.

Funding