Genetic inducible fate mapping in mouse: Establishing genetic lineages and defining genetic neuroanatomy in the nervous system

Abstract

A fascinating aspect of developmental biology is how organs are assembled in three dimensions over time. Fundamental to understanding organogenesis is the ability to determine when and where specific cell types are generated, the lineage of each cell, and how cells move to reside in their final position. Numerous methods have been developed to mark and follow the fate of cells in various model organisms used by developmental biologists, but most are not readily applicable to mouse embryos in utero because they involve physical marking of cells through injection of tracers. The advent of sophisticated transgenic and gene targeting techniques, combined with the use of site-specific recombinases, has revolutionized fate mapping studies in mouse. Furthermore, using genetic fate mapping to mark cells has opened up the possibility of addressing fundamental questions that cannot be studied with traditional methods of fate mapping in other organisms. Specifically, genetic fate mapping allows both the relationship between embryonic gene expression and cell fate (genetic lineage) to be determined, as well as the link between gene expression domains and anatomy (genetic anatomy) to be established. In this review, we present the ever-evolving development of genetic fate mapping techniques in mouse, especially the recent advance of Genetic Inducible Fate Mapping. We then review recent studies in the nervous system (focusing on the anterior hindbrain) as well as in the limb and with adult stem cells to highlight fundamental developmental processes that can be discovered using genetic fate mapping approaches. We end with a look toward the future at a powerful new approach that combines genetic fate mapping with cellular phenotyping alleles to study cell morphology, physiology, and function using examples from the nervous system. Developmental Dynamics 235:2376 -2385, 2006.

Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor

“…Thus, all of the Hh-responding cells detected in the proximal incisor are presumably responding to SHH produced by pre-ameloblasts in the labial epithelium. Lineage tracing studies demonstrate that hedgehog-responsive cells in the adult incisor are stem cells In contrast to label retention, which points to the possible presence of stem cells, inducible genetic lineage tracing permanently labels a cell and all of the progeny of that cell and is thus a method that definitively identifies adult stem cells (Joyner and Zervas, 2006;Haegebarth and Clevers, 2009). To test whether the Hh-responsive cells in the proximal mouse incisor are indeed stem cells that can give rise to differentiated cell types in the tooth over a long period of time, we genetically labeled Gli1-expressing cells and traced their descendants in vivo using Gli1-CreER T2 ;R26R mice (Ahn and Joyner, 2005).…”

Lentiviruses allow widespread and conditional manipulation of gene expression in the developing mouse brain

“…Temporal and spatial control of gene expression by site-specific recombination is perhaps the most versatile approach currently available to investigate gene function and to perform lineage tracing of progenitor cells in virtually any organ (Glaser et al, 2005;Joyner and Zervas, 2006;Morozov, 2008). However, this type of manipulation is laborious and time-consuming, requiring the generation of at least two transgenic mouse lines by which one provides tissue-specific expression of the recombinase (e.g.…”

A nonclassical bHLH–Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling

“…Tamoxifen (Sigma-Aldrich) was dissolved at a concentration of 20 mg/mL in sunflower oil and administered to pregnant females at 100 mg/kg (Joyner and Zervas 2006). Embryos were dissected for analysis 48 h after tamoxifen treatment.…”