The knowledge may help scientists understand why an increasing number of boys are being born with birth defects called hypospadias, which involve incomplete formation of the urethral tube, resulting in an abnormally placed urethral opening on the underside of the penis. About one in 250 children has a urethral tube defect, more than double the frequency of 30 years ago.
The cell cycle controls whether a cell continues to give rise to more cells or stop dividing and become specialized with a specific function to carry out. Humans begin life as a single fertilized egg cell that eventually gives rise to countless cells in an adult. As each cell divides it must proceed through a growth phase, replicate its DNA and divide again, or it can be instructed to stop dividing and perform a specific function.
When scientists deleted the Sonic hedgehog gene in specific tissues at different stages of external genital development, they discovered the cell cycle takes longer than it normally does -- about 14.4 hours instead of the usual 8.5 hours for these cells. As a result, fewer cells are produced and genital growth is reduced by about 75 percent. The shape of the genitals is also altered.
"In this case, embryos wind up with underdeveloped, malformed genitalia, and the reason is that it takes nearly twice as long to complete the cell cycle, limiting the number of cells available to build the structure. What is surprising is that the number of cells seems to underlie the shape," said Ashley Seifert, a postdoctoral associate in the department of biology in the College of Liberal Arts and Sciences and first author of the paper. "We did not just see a miniaturized version of the genitals, we observed patterning defects, from subtle changes to severe malformations."
Researchers had thought malformations might be explained because important shaping genes that sculpt the genita
|Contact: John Pastor|
University of Florida