Lineage Tracing Using Cux2-Cre and Cux2-CreERT2 Mice

•Transgene expression patterns from the Cux2 genetic locus depend on genetic background•Cux2 is expressed in a subset of radial glial cells•The vast majority of excitatory neocortical neurons fate mapped by Cux2-Cre are Satb2+•Cux2-CreERT2+ progenitors in the E11.5 dorsal ventricular zone generate Satb2+ neurons

SummaryUsing genetic fate-mapping with Cux2-Cre and Cux2-CreERT2 mice we demonstrated that the neocortical ventricular zone (VZ) contains radial glial cells (RGCs) with restricted fate potentials ( Franco et al., 2012). Using the same mouse lines, Guo et al. (2013) concluded that the neocortical VZ does not contain lineage-restricted RGCs. We now show that the recombination pattern in Cux2-Cre/CreERT2 mice depends on genetic background and breeding strategies. We provide evidence that Guo et al. likely reached different conclusions because they worked with transgenic sublines with drifted transgene expression patterns. In Cux2-Cre and Cux2-CreERT2 mice that recapitulate the endogenous Cux2 expression pattern, the vast majority of fate-mapped neurons express Satb2 but not Ctip2, confirming that a restricted subset of all neocortical projection neurons belongs to the Cux2 lineage. This Matters Arising paper is in response to Guo et al. (2013), published in Neuron. See also the Matters Arising Response paper by Eckler et al. (2015), published concurrently with this Matters Arising in Neuron.