Cell Identification and Cell Lineage Analysis - Caenorhabditis Elegans: Molecular Genetics and Development - page 322

(DIC), or by expression of transgenic fluorescent reporter genes. The small size
and rapid development of C. elegans mean that animals can develop while under
continuous observation, allowing cell lineages to be analyzed throughout embry-
onic and postembryonic development. Embryonic cell lineages can also be traced
semiautomatically using timelapse imaging of GFP-labeled nuclei. Analysis of
mutant cell lineages remains important for defining the roles of developmental
control genes.
I. Introduction
Cell lineage analysis refers to the tracing of cellular genealogies by following cell
divisions and migrations over time, beginning with specific progenitor cells and
ending with their postmitotic descendants. The development of almost all metazoan
animals can in principle be described as a lineage tree whose origin is the single-cell
zygote. However, the variability of normal development means that cell lineage
relationships can in general only be described in probabilistic terms. In contrast,
for some animal groups, including nematodes, molluscs, and tunicates, the pattern of
cell divisions throughout development is highly invariant between individuals. In
such animals, the invariant lineage constitutes a complete fate map of development
with single-cell resolution.
The first descriptions of nematode cell lineages began in the late 19th century and
were based on a series of fixed specimens. These studies established that the pattern
of embryonic cell divisions was virtually invariant from animal to animal. In some
cases, the cell lineage was thought to generate a fixed number of cells in the adult
(''cell constancy'' or eutely), or at least in certain tissues (''partial constancy'') ( van
Cleave, 1932 ). However, it was not until the development of Nomarski DIC micros-
copy in the late 1960s ( Allen et al., 1969; Padawer, 1968 ) that it became feasible to
observe cell divisions in live animals.
Using Nomarski DIC microscopy of live animals the complete cell lineage of
C. elegans from zygote to adult was delineated in a series of classic studies,
culminating in the complete description of the embryonic cell lineage in 1983
( Sulston et al., 1983 ). All these descriptions were based on direct observation of
live animals, without significant use of recording technology. Since then, cell
lineages have been traced in over ten other nematode species (see Table I ). The
C. elegans ''lineage papers'' ( Table II ) remain an essential resource for learning
cell identification and lineage analysis. For historical accounts of the early days of
lineage analysis see Horvitz and Sulston (1990) and John Sulston ' sNobelLecture
( Sulston, 2003 ).
With the advent of green fluorescent proteins (GFP) in the early 1990s
( Chalfie et al., 1994 ), cell identification entered a new phase. Now specific cells
or cell types could be identified more rapidly, without the need for meticulous
drawing out of cells and their positions. Expression of a fluorescent marker provided
an unambiguous measure of cell fate. For example, cells could be identified even