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Cell-cell interactions in cell fate determination in Caenorhabditis
What is the role of induction in cell fate determination?
C. elegans has similar advantages to Drosophila as a system
for the study of development: the exploitation of the power of genetics.
Furthermore the fates of each and every cell during development to the adult
are known (Sulston et al., 1983). Thus, cell fate studies can be
done very precisely. We shall examine the determination of pharyngeal fate
development as an example of the kinds of elegant developmental analyses
that are possible with C. elegans..
The first cleavage division generates a large anterior AB blastomere and
a smaller posterior P1 blastomere (Evans et al., 1994, Fig. 1). Descendants
of both AB and P1 produce pharyngeal cells during development. However,
they differ in their potential to produce these cells. P1 has an intrinsic
ability to produce pharyngeal cells when it is isolated from AB. However,
AB descendants only produce pharyngeal cells as a result of interactions
with P1 descendants, in a process that requires maternal expression of the
The GLP-1 protein is a transmembrane protein that is thought to function
as a receptor for extracellular signals. In embryos from homozygous glp-1
mutant mothers, P1 produces pharyngeal cells, but AB does not, indicating
that a glp-1-dependent signaling event is necessary for AB to produce
pharyngeal cells. This observation demonstrates how genetic tools can be
used to answer questions that would otherwise require manipulations of embryos.
The larger AB blastomere divides to produce ABa and ABp, whereas P1 divides
to yield EMS and P2. Of the two products of P1 division, only EMS retains
the ability to produce pharyngeal cells. The cells at this stage are situated
in the egg case such that P2 is adjacent to ABp and not ABa (see Fig. 1).
Thus, P2 and ABp can engage in cell-cell interactions that require glp-1.
At the next division, EMS divides to produce E and MS. The MS cell engages
in an inductive interaction that causes descendents of ABa to form anterior
pharynx. This interaction also requiresglp-1 . Because GLP-1 is a
thought to be receptor protein, it should be produced in descendants of
the anterior blastomere, which are the targets of these glp-1-dependent
Although the glp-1 mRNA is present in both
the oocyte and embryo, the GLP-1 protein is not synthesized in oocytes.
Is its synthesis generalized, or is it restricted to the anterior blastomeres?
The immunolocalization results shown in Figure 2 reveal that the protein
is strictly restricted to the anterior blastomeres. This localization occurs
in spite of the uniform distribution of the mRNA. Thus, the mRNA is subject
to spatially-restricted translation.
Because of the frequent involvement of 3' UTRs on translational regulation,
Evans et al. tested whether the 3' UTR of glp-1 is responsible
for its regulation. A reporter construct was made that had a ß-galactosidase
coding sequence and nuclear localization signal located upstream of a glp-1
3' UTR. (The nuclear localization signal allowed for the ß-gal to
accumulate in nuclei and be more readily detectable.) A control reporter
that lacked the glp-1 3' UTR was also used. RNA was synthesized in
vitro from either construct and injected into the germline.
As shown in Figure 5 (Evans et al., 1994), embryos derived from animals
injected with control RNA had lacZ staining throughout the embryo, whereas
those derived from animals injected with lacZglp-1 RNA had ß-gal staining
only in anterior blastomeres. However, the RNA itself was evenly distributed
within the embryos (Fig. 6). Thus, the glp-1 3' UTR is sufficient
to restrict translation to the anterior blastomeres. A deletion analysis
was conducted to identify the elements in the 3' UTR that regulate glp-1
translation. As shown in Table 1, a 125 nt element at the 3' end of the
UTR is necessary and sufficient for temporal regulation, whereas a 61 nucleotide
region in the middle of the 3' UTR is required for spatial regulation. (See
also Fig. 5G-5I.) These results indicate that the localization of GLP-1
protein is a consequence of translational regulation of glp-1 mRNA.
The role of induction in determination of cell fate in C. elegans
has only recently been appreciated. It had previously been thought that
cell fate was entirely a consequence of intrinsic differences among cells
due to localization of determinants. These inductive interactions operate
at the level of single cells, whereas inductive interactions in higher organisms
function at the tissue level.
- Diagram cleavage to the 8-cell stage. Label each cell and place on
your diagram the interactions that are necessary for the formation of the
- What is the role of GLP-1?
- What is the phenotype of embryos derived from homozygous glp-1
- How is synthesis of GLP-1 regulated? Describe experimental evidence.
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