The Questions of Developmental Biology

Cell-Cell Interactions and Chance in the Determination of Cell Types
The development of the vulva in C. elegans offers several examples of induction on the
cellular level. We have already discussed the reception of the EGF-like LIN-3 signal by the cells
of the equivalence group that can form the vulva. But before this induction occurs, there is an
earlier interaction that forms the anchor cell. The formation of the anchor cell is mediated by the
lin-12 gene, the C. elegans homologue of the Notch gene. In wild-type C. elegans
hermaphrodites, two adjacent cells, Z1.ppp and Z4.aaa, have the potential to become the anchor
cell. They interact in a manner that causes one of them to become the anchor cell while the other
one becomes the precursor of the uterine tissue. In recessive lin-12 mutants, both cells become
anchor cells, while in dominant mutations, both cells become uterine precursors (Greenwald et al.
1983). Studies using genetic mosaics and cell ablations have shown that this decision is made in
the second larval stage, and that the lin-12 gene only needs to function in that cell destined to
become the uterine precursor cell. The presumptive anchor cell does not need it. Seydoux and
Greenwald (1989) speculate that these two cells originally synthesize both the signal for uterine
differentiation (the LAG-2 protein, homologous to Delta in
Drosophila) and the receptor for this molecule (the LIN-12
protein, homologous to Notch) (Figure 6.30; Wilkinson et al.
1994). During a particular time in larval development, the cell
that, by chance, is secreting more LAG-2 causes its neighbor
to cease its production of this differentiation signal and to
increase its production of LIN-12 protein.
The cell secreting LAG-2 becomes the gonadal anchor cell,
while the cell receiving the signal through its LIN-12 protein
becomes the ventral uterine precursor cell. Thus, the two cells
are thought to determine each other prior to their respective
differentiation events.
The anchor cell/ventral uterine precursor decision
illustrates two important aspects of determination in two
originally equivalent cells. First, the initial difference
between the two cells is created by chance. Second, this
initial difference is reinforced by feedback.
Such a mechanism is also seen in the determination of which
of the originally equivalent epidermal cells of the insect
embryo will generate the neurons of the peripheral nervous
system. Here, the choice is between becoming a skin
(hypodermal) cell or a neural precursor cell (a neuroblast). The Notch gene of Drosophila, like
its C. elegans homologue, lin-12, channels a bipotential cell into one of two alternative paths.
The LIN-12 protein will be used again during vulva formation. It is activated by the primary
vulval lineage to stop the lateral vulval cells from forming the central vulval phenotype (Figure
6.19).
Soon after gastrulation, a region of about 1800 ectodermal cells lies along the ventral
midline of the Drosophila embryo. These cells, known as neurogenic ectodermal cells, all have
the potential to form the ventral nerve cord of the insect. About one-quarter of these cells will
become neuroblasts, while the rest will become the precursors of the hypodermis. The cells that
give rise to neuroblasts are intermingled with those that become hypodermal precursors. Thus,
each neurogenic ectoderm cell can give rise to either hypodermal or neural precursor cells
(Hartenstein and Campos-Ortega 1984).