Lineage Tracing Using Cux2-Cre and Cux2-CreERT2 Mice

Using genetic fate-mapping with Cux2-Cre and Cux2-CreERT2 mice we demonstrated that the neocorticalventricular zone (VZ) contains radial glial cells (RGCs) with restricted fate potentials (Franco etal., 2012). Using the same mouse lines, Guo etal. (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 etal. 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 etal. (2013), published in Neuron. See also the Matters Arising Response paper by Eckler etal. (2015), published concurrently with this Matters Arising in Neuron.