Absent mouse gene leads to no-brainer.

Scientists who shut off a certain gene in developing mice got a bizarre result: The mice look normal from tail to neck, but for a head they have only a stump tipped with ears.

These mice "unambiguously show that this is an essential gene" for early embryo development, says developmental biologist William Shawlot. The work by Shawlot and Richard R. Behringer of the University of Texas' M.D. Anderson Cancer Center in Houston also verifies a 70-year-old notion that a tiny region of the embryo touches off changes in neighboring tissue that cause it to grow into a major part of the neural system.

An embryo begins as a clump of identical cells, but soon control genes switch on, setting off reaction cascades that cause this bit of tissue to become the heart, that bit a limb, and so on.

Scientists have begun unraveling how control genes work by seeing what happens when they "knock out," or disable, them. Shawlot and Behringer knew from work on a similar gene in Xenopus frogs that a mouse gene called Lim1 probably plays a role in head development.

They replaced Lim1 in immature mouse cells, called stem cells, with a nonfunctional gene. They then inserted the cells into mouse embryos and eventually bred mice that carried two copies of the gene.

Most of these mice died as embryos at about 10 days of gestation, the scientists report in the March 30 Nature. The embryos had a normal tail, trunk, and limbs but lacked most of the head. A more graphic demonstration of the gene's effect came from a handful of headless mice (4 of more than 1,000 born) that survived the 19 days until birth, when they emerged stillborn.

The mice had most of the hindbrain but lacked forebrain and midbrain. Possession of those areas distinguishes vertebrates, including fish, reptiles, and people, from other animals.

The Lim1 result jibes with Nobel prize-winning work by German embryologist  Hans Spemann in the 1920s. Spemann transferred a patch of tissue from one newt embryo to another and caused the second embryo to form an extra central nervous system. Realizing that the transplanted tissue could direct how adjacent cells develop, he called the potent region it came from the "organizer."

"The important point is that this embryological concept developed by Spemann is, in fact, true," Shawlot says.

"The organizer has been considered the soul of the vertebrate embryo," notes Eddy M. De Robertis of the Howard Hughes Medical Institute at the University of California, Los Angeles. "These are very old problems in biology and very fundamental ones. Now new progress is being made. A biochemical pathway is now being established as to how this organizer works." De Robertis wrote a commentary accompanying the paper.

Scientists have knocked out several organizer genes in mice in recent years but saw mostly trunk or tail effects. "A headless embryo like that has not been seen," De Robertis says. "It suggests that there is a different regulatory pathway to the formation of the head than to the formation of the trunk-tail. This we didn't know -- that there could be two genetic mechanisms."

The Lim1 gene probably has no connection with such human defects as babies born with only part of a brain, a result of the neural tube failing to close properly. But, De Robertis says, "this is the type of thing that will tell you about how Siamese twins occur."

Shawlot and Behringer write that the headless mouse "will be an important genetic tool for the molecular and cellular analysis" of neural development in vertebrate embryos.