vertebra,sometimes the loss of one in the lower back; either way, homeotic transformations are much like the segment transformations that geneticists seek in their mutant flies.
It is no surprise, then, that the identity of each vertebra is controlled by homeotic genes much like those that keep a fly’s segments in order. Of course, matters are rather more complicated for us. Flies have only eight homeotic genes while mammals have thirty-nine, so many that the evocative Latinate names have been dropped: no Ultrabithorax or proboscipedia for us, but only the prefix Hox followed by unmemorable letters and digits: Hoxa3, Hoxd13 and so on. In mammals, as in flies, homeotic genes begin their work early in the life of the embryo. Vertebrae develop from blocks of mesoderm called somites that form on either side of the nerve cord like rows of little bricks. Each homeotic protein is present in just some of the somites. All thirty-nine are present in the tail somites, but then they fall away, in ones and twos, so that finally only a handful remain in the somites closest to the head. The vertebral calculator is not very economical. For the seventh neck vertebra it looks something like this:
If Hoxa4 is present
And Hoxa5 is present
And Hoxb5 is present
And Hoxa6 is present
And Hoxb6 is present
And all other posterior Hox genes are absent
Then a seventh neck vertebra will form: NO RIBS
Should a mutation cripple any one of the genes that encode these five proteins, the seventh vertebra will transform into its neighbour, the eighth vertebra, and gain a pair of ribs.
S OMITES IN A HUMAN EMBRYO . F ROM F RANZ K EIBEL 1908
Normentafel zur Entwicklungsgeschichte des Menschen.
Distinguishing one vertebra from another is merely one instance of a problem that the embryo must solve repeatedly: the differentiation of parts along the head-to-tail axis. The embryo must solve this problem for the neural tube, uniform at first, but which later forms a brain at one end. It must solve it for the bones of the head – so that maxillae are formed next to mandibles and each is attached to its appropriate nerves and muscles. And it must solve this problem for the gut tube that becomes the stomach, liver, pancreas and intestines as well as theventral blood vessel that becomes the four chambers of the heart. The Hox gene calculator is involved in all this.
How it works in mammals is known from mice in which one or more Hox genes have been deleted. Such mice are often profoundly disordered. Some have fore-limbs that are strangely close to their heads; others are missing parts of their hindbrains or cranial nerves. Some have hernias that cause their intestines to bulge into their thoracic cavities, or else open neural tubes. Some are missing their thymus, thyroid and parathyroid glands and have abnormal hearts and faces; some walk on their toes instead of on the soles of their feet, even as their hindquarters convulse uncontrollably. Most mice in which even one Hox gene has been deleted die young.
The Hox gene calculator is thought to work in humans in much the same way. The evidence for this belief is indirect and comes from a single 1997 study in which a group of London researchers stained six RU486 – ‘morning after pill’ – aborted embryos with molecular probes to reveal the times and place of homeotic gene expression. The embryos were four weeks old, about five millimetres long, and came from unwanted pregnancies. In autoradiographs of the sliced and stained embryos, Hox gene activity appears as grainy streaks and patches of white against the dark outlines of nascent rhombocephalons and pharyngeal arches. The patterns of Hox gene activity are just what one would expect from mice.
This is important and gratifying to know. But the study has not been repeated. Studies on human embryos are rare. In the United Kingdom they can only be done once formidableregulatory hurdles have been cleared; in the United States they can’t be done at all,
It is no surprise, then, that the identity of each vertebra is controlled by homeotic genes much like those that keep a fly’s segments in order. Of course, matters are rather more complicated for us. Flies have only eight homeotic genes while mammals have thirty-nine, so many that the evocative Latinate names have been dropped: no Ultrabithorax or proboscipedia for us, but only the prefix Hox followed by unmemorable letters and digits: Hoxa3, Hoxd13 and so on. In mammals, as in flies, homeotic genes begin their work early in the life of the embryo. Vertebrae develop from blocks of mesoderm called somites that form on either side of the nerve cord like rows of little bricks. Each homeotic protein is present in just some of the somites. All thirty-nine are present in the tail somites, but then they fall away, in ones and twos, so that finally only a handful remain in the somites closest to the head. The vertebral calculator is not very economical. For the seventh neck vertebra it looks something like this:
If Hoxa4 is present
And Hoxa5 is present
And Hoxb5 is present
And Hoxa6 is present
And Hoxb6 is present
And all other posterior Hox genes are absent
Then a seventh neck vertebra will form: NO RIBS
Should a mutation cripple any one of the genes that encode these five proteins, the seventh vertebra will transform into its neighbour, the eighth vertebra, and gain a pair of ribs.
S OMITES IN A HUMAN EMBRYO . F ROM F RANZ K EIBEL 1908
Normentafel zur Entwicklungsgeschichte des Menschen.
Distinguishing one vertebra from another is merely one instance of a problem that the embryo must solve repeatedly: the differentiation of parts along the head-to-tail axis. The embryo must solve this problem for the neural tube, uniform at first, but which later forms a brain at one end. It must solve it for the bones of the head – so that maxillae are formed next to mandibles and each is attached to its appropriate nerves and muscles. And it must solve this problem for the gut tube that becomes the stomach, liver, pancreas and intestines as well as theventral blood vessel that becomes the four chambers of the heart. The Hox gene calculator is involved in all this.
How it works in mammals is known from mice in which one or more Hox genes have been deleted. Such mice are often profoundly disordered. Some have fore-limbs that are strangely close to their heads; others are missing parts of their hindbrains or cranial nerves. Some have hernias that cause their intestines to bulge into their thoracic cavities, or else open neural tubes. Some are missing their thymus, thyroid and parathyroid glands and have abnormal hearts and faces; some walk on their toes instead of on the soles of their feet, even as their hindquarters convulse uncontrollably. Most mice in which even one Hox gene has been deleted die young.
The Hox gene calculator is thought to work in humans in much the same way. The evidence for this belief is indirect and comes from a single 1997 study in which a group of London researchers stained six RU486 – ‘morning after pill’ – aborted embryos with molecular probes to reveal the times and place of homeotic gene expression. The embryos were four weeks old, about five millimetres long, and came from unwanted pregnancies. In autoradiographs of the sliced and stained embryos, Hox gene activity appears as grainy streaks and patches of white against the dark outlines of nascent rhombocephalons and pharyngeal arches. The patterns of Hox gene activity are just what one would expect from mice.
This is important and gratifying to know. But the study has not been repeated. Studies on human embryos are rare. In the United Kingdom they can only be done once formidableregulatory hurdles have been cleared; in the United States they can’t be done at all,
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