The Questions of Developmental Biology

The distal tip cell extends long
filaments that touch the distal germ
cells. The extensions contain in their cell
membranes the Lag-2 protein, a C.
elegans homologue of Delta (Henderson
et al. 1994; Tax et al. 1994; Hall et al.
1999). The Lag-2 protein maintains
these germ cells in mitosis and inhibits
their meiotic differentiation.
Austin and Kimble (1987)
isolated a mutation that mimics the
phenotype obtained when the distal tip
cells are removed. It is not surprising
that this mutation encodes Glp-1, the C.
elegans homologue of Notch the
receptor for Delta. All the germ cell
precursors of nematodes homozygous for the recessive mutation glp-1 initiate meiosis, leaving no
mitotic population. Instead of the 1500 germ cells usually found in the fourth larval stage of
hermaphroditic development, these mutants produce only 5 to 8 sperm cells. When genetic
chimeras are made in which wild-type germ cell precursors are found within a mutant larva, the
wild-type cells are able to respond to the distal tip cells and undergo mitosis. However, when
mutant germ cell precursors are found within wild-type larvae, they all enter meiosis. Thus, the
glp-1 gene appears to be responsible for enabling the germ cells to respond to the distal tip cell's
signal.*
After the germ cells begin their meiotic divisions, they still must become either sperm or
ova. Generally, in each ovotestis, the most proximal germ cells produce sperm, while the most
distal (near the tip) become eggs (Hirsh et al. 1976). This means that the germ cells entering
meiosis early become sperm, while those entering meiosis later become eggs. The genetics of this
switch are currently being analyzed. The laboratories of Hodgkin (1985) and Kimble (Kimble et
al. 1986) have isolated several genes needed for germ cell pathway selection, but the switch
appears to involve the activity or inactivity of fem-3 mRNA. Figure 19.16 presents a scheme for
how these genes might
function.