Phenotypic analysis with trans-recombination-based genetic mosaic models.

Mosaicism refers to the presence of genetically distinct cell populations in an individual derived from a single zygote, which occurs during the process of development, aging, and genetic diseases. To date, a variety of genetically engineered mosaic analysis models have been established and widely used in studying gene function at exceptional cellular and spatio-temporal resolution, leading to many ground-breaking discoveries. Mosaic analysis with a repressible cellular marker (MARCM) and mosaic analysis with double markers (MADM) are genetic mosaic analysis models based on trans-recombination. These models can generate sibling cells of distinct genotypes in the same animal and simultaneously label them with different colors. As a result, they offer a powerful approach for lineage tracing and studying the behavior of individual mutant cells in a wildtype environment, which is particularly useful for determining whether gene function is cell autonomous or non-autonomous. Here, we present a comprehensive review on the establishment and applications of MARCM and MADM systems. Leveraging the capabilities of these mosaic models for phenotypic analysis will facilitate new discoveries on the cellular and molecular mechanisms of development and disease.