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0:00
My name is DJ Pan, I am a faculty member
in the Department of Molecular Biology and
Genetics at Johns Hopkins
University School of Medicine.
In today's lecture I will
review recent studies
in the fruit fly Drosophila concerning
the control of tissue growth.
In particular my lecture will focus
on the recent elucidation of a novel
signalling pathway which we
call the 'Hippo pathway'.
It's my hope that this lecture will
provide you with an example of how one can
use the fruit fly as a powerful model
to understand the basic mechanisms of
human disease,
including the mechanisms of human cancer.
0:41
During organogenesis, growth and
patterning must be independently
coordinated in order to generate
organs of reproducible size and shape.
Compared to our understanding
of pattern formation,
relatively less is known about how
the size of an organ is determined.
The compound eye of Drosophila is
an ideal system to study organ size,
since this organ is totally
dispensable for animal viability.
This means one can screen for
mutations that increase or
decrease the size of an eye
without worrying about
the detrimental effects of
the mutation on animal viability.
1:22
In the last decade, many Drosophila
labs have conducted genetic screens for
growth regulators of the compound
eye using mosaic flies.
The essence of these screens is to
generate, by mitotic recombination,
a cell that is homozygous for
a given mutation in an otherwise
heterozygous mutant background.
These screens are set up in such a way
that whenever a homozygous mutant
cell (designated here as minus
over minus or -/-) is generated,
a sibling cell is also generated which
has a plus over plus (+/+) genotype.
This pair of cells then proliferates
to generate two clones of cells next to
each other in the adult eye.
If a gene does not play
a role in tissue growth,
we might expect the mutant clone to be
of the same size as a sibling clone.
However if a gene normally is positively
required for tissue growth we
might expect the mutant clone to
be smaller than the sibling clone.
On the contrary, if a gene normally
plays a negative role in growth control
then we might expect a mutant clone
to be larger than the sibling clone.
This last class of overgrown mutation
represents what we call the tumor
suppressor genes.
