The cluster of seemingly nondescript cells that grows into a chick has a stronger sense of identity than you'd think. Rather than waiting for hormonal cues from the sex organs, the cells know whether they're male or female from the start, a new study reveals. The discovery challenges the standard picture of how sexual differences develop in vertebrates.
In humans, somatic cells—the generic cells that grow into muscle, bone, and organs—start off unisex. Even though chromosomes mark the cells as male or female, they don't head down that path until after the gonads—testes in a male, ovaries in a female—begin developing and secreting hormones at about 7 weeks. Sex is decided at this point by a key gene on the male-specific Y chromosome, which signals the embryo to develop testes. Hormones then drive the erstwhile unisex cells to develop male or female features.
For the past 50 years, biologists assumed that all vertebrates needed these cues before their cells took on a male or female identity. So Michael Clinton, a developmental biologist at the University of Edinburgh in the United Kingdom, couldn't understand why it was so difficult to find the key sex-determining gene in chicken chromosomes. Then he got a call from an industry acquaintance who on his visits to poultry breeders occasionally noticed strange birds that were half brown and half white and had an oddly lopsided breast. Clinton agreed to take a look.
The chickens were gynandromorphs, with their sex split down the middle. They appeared male on one side and female on the other. Unlike humans, where women have two X chromosomes and men have an X and a Y, male chickens normally have two Z chromosomes, whereas females have a Z and a W chromosome. Clinton’s team sampled blood and skin from both sides of each chicken, expecting to find that cells from one side or the other lacked a sex chromosome. This might give them a clue as to which chromosome, the Z or the W, held the key gene for determining sex-specific traits, Clinton thought.
"It turned out that was completely rubbish," Clinton says. Both sides of the chickens included normal male (ZZ) and female (ZW) cells. But male cells dominated one side, whereas female cells dominated the other, accounting for the split appearance. The same was true of cells taken from the chickens' breast muscles and wattles.
This result suggested that chicken cells, unlike mammalian cells, had their own sex identity that was to some extent independent of what hormones the gonads produced. Studies of normal chicken embryos bolstered the case. Just 18 hours after fertilization, long before gonads began to form, the embryos exhibited either "maleness" or "femaleness," as indicated by expression of sex-specific RNA molecules. To test whether these cells were really male or female, the team also removed them from early embryos that hadn't formed gonads yet and delicately placed them in eggs containing male and female chicks, creating partial gynandromorphs. After a week, some implanted cells had become part of the gonads of the opposite-sex host. But they resolutely held on to their sex identities, the team reports in tomorrow's issue of Nature.
So instead of waiting for a cue from the gonads, somatic cells in chickens seem to know their own sex. The researchers speculate that the cells somehow drive masculine or feminine development, probably by triggering or repressing the activity of a gene called DMRT-1 on the Z chromosome. Last year, researchers found that suppressing this gene in male chick embryos made them develop a testis with feminine characteristics.
Although scientists had begun to suspect that the standard mammalian model for sex determination wasn't the whole story for all vertebrates, "this study very clearly shows it for the first time certainly in birds," says Craig Smith, a developmental biologist at the Murdoch Childrens Research Institute in Parkville, Australia, whose team discovered DMRT-1. The mechanism "might be more pervasive amongst animals than we've thought."