Manipulating gene activity in Wnt1-expressing precursors of neural epithelial and neural crest cells.

Targeted gene disruption or expression often encounters lethality. Conditional approaches, permitting manipulation at desired stages, are required to overcome this problem in order to analyze gene function in later developmental processes. Wnt1 has been shown to be expressed in neural crest precursors at the dorsal midline region. However, its expression was not detected in emigrated neural crest cells, the descendants of Wnt1-expressing precursors. We have developed mouse transgenic systems to manipulate gene activity in the Wnt1-expressing precursors and their derivatives by integrating the tetracycline-dependent activation and Cre-mediated recombination methods. A new Wnt1-rtTA strain, carrying rtTA under control of Wnt1 regulatory elements, has been created for gene manipulation in a spatiotemporal-specific fashion. Together with our previously developed Wnt1-Cre;R26STOPrtTA model, these systems permit conditional gene expression and ablation in pre-migratory and/or post-migratory neural crest cells. This study demonstrated the versatility of our mouse models to achieve gene manipulation in early neural development. (c) 2009 Wiley-Liss, Inc.