OVERVIEW
My laboratory is focused on the process
of sex determination. In mammals the
embryonic gonad can develop into a
testis or ovary. Sex determination
is the step at which the gonad and
its store of germ cells initiate male
or female development. Once the gonad
is committed to the testis or ovarian
pathway, the production of male or
female hormones controls the development
of all other sexually dimorphic characteristics.
CURRENT PROJECTS
1. Sertoli-Germ Cell Interactions
Sertoli/
germ cell interactions represent
a classic model of the stem cell
niche. Germ cells are a critical
stem cell population of the body
and their interactions with the
somatic cells that regulate their
development has been a source of
many advances in stem cell biology.
Regulation of germ cell development
is significantly different in XX
and XY gonads from the earliest
time when sex determination is
initiated. Work on molecular signaling
pathways that control this process
will continue in the lab.
2. The Battle of the Sexes: Integration
of Intra- and Extra-Cellular Signals
We
have made progress in identifying
the downstream regulatory pathways
in testis development; however,
we know almost nothing about the
steps immediately downstream of
Sry that commit the progenitor
cell population in the gonad to
the Sertoli fate. Recent evidence
in the lab has led us to hypothesize
that FGF9 and WNT4 are opposing
extracellular signaling pathways
that operate in parallel to intracellular
pathways to establish the male
or female fate of the gonad. Work
in the lab centers on defining
the relationship between FGF9 signaling,
cell division, SRY expression,
and the initiation of Sertoli cell
differentiation.
3. Temperature Dependent Sex Determination
We
plan to primarily use the mouse
as a model system, but we will
also investigate the process of
gonadal fate determination in the
red-eared slider turtle, a temperature
dependent sex-determination system.
We intend to investigate the role
of FGF9 and WNT4 signaling in establishing
the testis or ovarian fate in turtle
gonads.
4. The Role of the Vasculature in
Testis Development
As
a result of our work on cell migration,
we learned that the formation of
the male-specific vasculature plays
an important role in testis development.
To facilitate the study of the
role of vascular development in
testis formation, we are imaging
the migration of live, GFP-labeled
endothelial cells into the testis
over a 48 hour period when testis
determination occurs and testis
cords assemble.
