Specific and spatial labeling of P0â Cre versus Wnt1â Cre in cranial neural crest in early mouse embryos

Abstract

P0â Cre and Wnt1â Cre mouse lines have been widely used in combination with loxPâ flanked mice to label and genetically modify neural crest (NC) cells and their derivatives. Wnt1â Cre has been regarded as the gold standard and there have been concerns about the specificity of P0â Cre because it is not clear about the timing and spatial distribution of the P0â Cre transgene in labeling NC cells at early embryonic stages. We reâ visited P0â Cre and Wnt1â Cre models in the labeling of NC cells in early mouse embryos with a focus on cranial NC. We found that R26â lacZ Cre reporter responded to Cre activity more reliably than CAAGâ lacZ Cre reporter during early embryogenesis. Cre immunosignals in P0â Cre and reporter (lacZ and RFP) activity in P0â Cre/R26â lacZ and P0â Cre/R26â RFP embryos was detected in the cranial NC and notochord regions in E8.0â 9.5 (4â 19 somites) embryos. P0â Cre transgene expression was observed in migrating NC cells and was more extensive in the forebrain and hindbrain but not apparent in the midbrain. Differences in the Cre distribution patterns of P0â Cre and Wnt1â Cre were profound in the midbrain and hindbrain regions, that is, extensive in the midbrain of Wnt1â Cre and in the hindbrain of P0â Cre embryos. The difference between P0â Cre and Wnt1â Cre in labeling cranial NC may provide a better explanation of the differential distributions of their NC derivatives and of the phenotypes caused by Creâ driven genetic modifications.