Decisions, decisions: Male or female?

August 26, 2005

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 eggs.

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 activator transcription.")

"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," said Mark Van Doren, assistant professor in the Department of Biology in the university's Krieger School of Arts and Sciences. "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 post-doctoral 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 identity.

"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."
-end-
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.

Digital photos of the researchers are available upon request. Contact Lisa De Nike.

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