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2010 ; 477
(ä): 153-81
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Genetic fate mapping using site-specific recombinases
#MMPMID20699142
Legué E
; Joyner AL
Methods Enzymol
2010[]; 477
(ä): 153-81
PMID20699142
show ga
Understanding how cells are assembled in three dimensions to generate an organ,
or a whole organism, is a pivotal question in developmental biology. Similarly,
it is critical to understand how adult stem cells integrate into an existing
organ during regeneration or in response to injury. Key to discovering the
answers to these questions is being able to study the various behaviors of
distinct cell types during development or regeneration. Fate mapping techniques
are fundamental to studying cell behaviors such as proliferation, movement, and
lineage segregation, as the techniques allow precursor cells to be marked and
their descendants followed and characterized over time. The generation of
transgenic mice, combined with the use of site-specific recombinases (SSR) in the
mouse genome, has provided a means to develop powerful genetic fate mapping
approaches. A key advantage of genetic fate mapping is that it allows cells to be
genetically marked, and therefore the mark is transmitted to all the descendants
of the initially marked cells. By making modifications to the SSRs that render
their enzymatic activity inducible, and the development of an assortment of
reporter alleles for marking cells, increasingly sophisticated genetic fate
mapping studies can be performed. In this chapter, we review the four main
genetic fate mapping methods that utilize intrachromosomal recombination to mark
cells (cumulative, inducible, clonal, and intersectional) and one
interchromosomal method, the tools required to carry out each approach, and the
practical considerations that have to be taken into account before embarking on
each type of genetic fate mapping study.