Worm Breeder's Gazette 5(1): 27

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Control of Differentiation and Spatial Organization of Germ Cells

J. Kimble

Two descendants of the gonadal somatic precursor cells, Z1 and Z4, 
appear to regulate germ cell development in both sexes.  These two 
cells - the distal tip cells - arise in homologous positions in the Z1-
Z4 lineage during L1.  In hermaphrodites, one distal tip cell resides 
at the growing tip of each gonadal arm.  In males, both distal tip 
cells reside at the stationary end, and the linker cell precedes the 
elongating tip.  Ablation of both distal tip cells has two effects on 
germ cell development in both sexes : divisions cease among all 
descendants of the germ cell precursors, Z2 and Z3, and all Z2 and Z3 
descendants enter meiosis.  In hermaphrodites, ablation of the distal 
tip cell(s) stops elongation of the relevant gonadal arm.  In males, 
the elongation or leader function is allocated to a different somatic 
cell, the linker cell.  When the linker cell is destroyed, elongation 
is blocked, but proliferation of the germ cells continues to generate 
a large oval mass instead of a reflexed tube.
The laser ablation experiments reported here address three questions 
concerning the control of germ cell development: 1) Is the primary 
function of the distal tip cells stimulation of mitosis or suppression 
of meiosis?  2) How is the spatial organization of the germ cell 
component of the gonad established and maintained?  3) Is the 
sperm/oocyte decision in hermaphrodites made according to a lineage 
mechanism?
In the intact animal, the distal tip cells might stimulate mitosis 
which secondarily suppresses entry into meiosis, or they might 
suppress entry into meiosis which secondarily permits proliferation of 
the germ cells.  Superficially, these two possibilities seem difficult 
to distinguish.  However, because germ cells become meiotic at a 
characteristic point in development, one can ask how that time of 
entry is affected by various experimental manipulations.  Such 
knowledge can be used to infer what role the distal tip cells play in 
the decision of Z2-Z3 descendants to enter meiosis.
The following experiments suggest that the primary function of the 
distal tip cells is to suppress meiosis.  After ablation of the distal 
tip cells as early as possible in L1 the germ cells undergo 2-3 rounds 
of division and enter meiosis at approximately the same time as in 
unoperated animals.  After ablation of the distal tip cells during L2, 
the germ cells undergo no more than one round of division and, again, 
enter meiosis at the appropriate time.  If the distal tip cells serve 
a purely mitogenic function, one would expect to detect meiotic nuclei 
earlier than normal in these experiments, and one would expect the 
germ cells to stop dividing after an equivalent number of divisions in 
all experiments.  However, if the distal tip cells primarily suppress 
meiosis, one would expect the germ cells to continue to divide until 
signalled to enter meiosis if the distal tip cells had been ablated.  
A second experiment is consistent with this hypothesis.  It is 
possible to extend the time during which the distal tip cells 
influence the germ cells by reducing the number of germ cells early 
during development.  For example, if Z2 or Z3 is ablated just after 
hatching, the number of germ cells is effectively reduced by half at 
any time during gonadogenesis.  Such experiments show that entry into 
meiosis can be delayed significantly by reducing the size of the gonad 
and thereby bringing the distal tip closer to the most proximal point 
in the germ cell tube.
The effect of the distal tip cells on germ cells also sheds light on 
how the polarity and spatial organization of a gonadal arm is 
established and maintained.  In the adult, the germ cells are arranged 
to display a progression of maturation along the distal-proximal axis, 
with mitotic cells located most distally and the most mature meiotic 
cells found most proximally.  This organization is established and 
maintained when all the gonadal somatic cells except the distal tip 
cells are ablated during L1.  In contrast, ablation of the distal tip 
cells severely disrupts that organization.  It therefore seems likely 
that the distal tip cells are responsible for establishing the 
polarity of the germ cell component of the gonad.  The most appealing 
mechanism for this is that, as distal tip cells become positioned 
progressively further away from the proximal end, germ cells escape 
their influence and enter meiosis.  Such a scheme would produce the 
gradient of maturation observed in the gonad.
The ability to manipulate the number of germ cells made (by ablation 
of the distal tip cells) has been used to study the sperm oocyte 
decision in hermaphrodites.  If ablation of both distal tip cells is 
performed during L1 or L2, all the germ cells made differentiate as 
sperm.  This means that no oocyte precursor is set aside irreversibly 
early during development.  Since the decision whether or not to 
produce oocytes seems to be made during L1, based on shift experiments 
of the ts transformer mutant B202, this argues that a lineage 
mechanism is not relevant to this decision.  When the distal tip cells 
are ablated later and later, the number of sperm precursor cells 
increases until the normal complement of sperm is made per arm.  Once 
this number is reached one begins to see oocyte differentiation.  
Experiments are in progress to try to understand how the number of 
sperm precursor cells is determined.