Johns Hopkins biologists have determined how
developing embryos tell their specialized "germ cells"
whether to develop into a male's sperm or a female's
Present in both male and female embryos, germ cells
are the precursors to both sperm and eggs. Unable to
"decide" on their own which to become, however, germ cells
must take "advice" from other cells within embryos as to
which is the appropriate sex. The Johns Hopkins researchers
have found that this advice is delivered by a sequence of
chemical reactions called the JAK/STAT pathway. (JAK/STAT
is an acronym for Janus kinase/signal transducer and
"Though we all know that the survival of the species
depends on producing children, up until now we haven't
understood how germ cells in the developing embryos decide
whether to eventually become the sperm or eggs needed later
for adult reproduction," Mark Van Doren, assistant
professor in the
Department of Biology in the Krieger School of Arts and
Sciences, said. "Now we know one way these other cells are
talking to germ cells about sex."
Van Doren was co-author of the study, published in the
July 28 issue of the journal Nature. The discovery
promises to enhance understanding of infertility and even
some forms of cancer and could eventually lead to the
development of more effective treatments for both.
Led by Van Doren and postdoctoral fellow Matthew
Wawersik, the Johns Hopkins team used specialized
microscopes at the university's Integrated Imaging Center
to look at certain molecules and cell types in fruit fly
embryos. Though they already knew that the JAK/STAT pathway
was an important means of various types of cell-to-cell
communication, they discovered that embryos also were using
that pathway to send germ cells signals regarding sexual
"This work implicates that pathway as a key regulator
of early decisions made by germ cells as to whether to
eventually develop into eggs or sperm," Wawersik said.
Though the team's observations were limited to the
pathway's role in fruit fly germ cell communication, Van
Doren said the same conduit also is active in humans and
mice. When communication via the JAK/STAT pathway misfires,
diseases such as cancer can result, he said.
"Evolutionarily, germ cells are one of the most
ancient cell types, needed by every type of animal to
reproduce," Van Doren said. "Their developmental program is
very similar, whether we are talking fruit flies or humans.
As a result, these findings could eventually help us
understand and treat defects in germ cell development that
lead to human infertility and disease."
The team's work was supported by the National
Institutes of Health and the Association of Regulatory and
Clinical Scientists, as well as by an NIH National Research
Service Award postdoctoral fellowship.