Lineage Tracing Using Cux2-Cre and Cux2-CreERT2 Mice

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Radial glial cells (RGCs) are neural stem cells in the developing neocortex.
• Previous studies using Cux2-Cre/CreERT2 mice yielded conflicting conclusions regarding RGC lineage restriction.
• Discrepancies may arise from variations in genetic background and transgene expression patterns.

Purpose of the Study:

• To clarify the lineage potential of RGCs in the neocortical ventricular zone (VZ).
• To reconcile conflicting findings regarding RGC lineage restriction in Cux2-Cre/CreERT2 mouse models.

Main Methods:

• Genetic fate-mapping using Cux2-Cre and Cux2-CreERT2 mouse lines.
• Analysis of recombination patterns influenced by genetic background and breeding strategies.
• Validation of endogenous Cux2 expression patterns in transgenic mouse sublines.

Main Results:

• Recombination patterns in Cux2-Cre/CreERT2 mice are dependent on genetic background and breeding.
• Transgenic sublines with drifted transgene expression likely led to previous conflicting conclusions.
• Fate-mapped neurons predominantly express Satb2 and not Ctip2, confirming Cux2 lineage restriction.

Conclusions:

• The neocortical VZ contains RGCs with restricted fate potentials.
• The Cux2 lineage contributes to a specific subset of neocortical projection neurons.
• Accurate recapitulation of endogenous gene expression is crucial for reliable fate-mapping studies.