Hox signals death for neuronal precursors
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《细胞学杂志》
Gould/Elsevier
The number of neurons in an adult fly is determined by a death-inducing blast of a homeodomain protein, based on results from Bruno Bello, Frank Hirth, and Alex Gould (National Institute for Medical Research, UK).
When the fly larva hatches, neurons are nearly evenly distributed along the major body axis. But in the adult, they are more numerous in the segments of the thorax than the abdomen, in part because neural stem cells (NSCs) in the thorax divide for a longer period of time. The new article describes "how division is stopped in its tracks and why this happens earlier in the abdomen than in the thorax," says Gould.
His group has found that a pulse of an abdomen-specific Hox transcription factor, called AbdA, in late larval stage NSCs determined the final number of neurons. Rather than signaling exit from the cell cycle, AbdA limited proliferation by inducing cell death through the grim/hid/reaper pathway. Artificial premature expression of AbdA further decreased the number of abdominal neurons by inducing early cell death.
Ectopic expression of thorax-specific Hox genes Antp and Ubx also induced NSC apoptosis. However, these genes were not normally expressed in thoracic NSCs, thus allowing the cells to propagate longer. Gould is now looking for more players in the Hox-induced death pathway, including factors that induce AbdA expression. He is also interested in features of NSCs that make them sensitive to Hox-induced apoptosis, even while many other Hox-expressing cell types are spared.
Reference:
Bello, B., et al. 2003. Neuron. 37:209–219.(Preventing apoptosis (right) enables an )
The number of neurons in an adult fly is determined by a death-inducing blast of a homeodomain protein, based on results from Bruno Bello, Frank Hirth, and Alex Gould (National Institute for Medical Research, UK).
When the fly larva hatches, neurons are nearly evenly distributed along the major body axis. But in the adult, they are more numerous in the segments of the thorax than the abdomen, in part because neural stem cells (NSCs) in the thorax divide for a longer period of time. The new article describes "how division is stopped in its tracks and why this happens earlier in the abdomen than in the thorax," says Gould.
His group has found that a pulse of an abdomen-specific Hox transcription factor, called AbdA, in late larval stage NSCs determined the final number of neurons. Rather than signaling exit from the cell cycle, AbdA limited proliferation by inducing cell death through the grim/hid/reaper pathway. Artificial premature expression of AbdA further decreased the number of abdominal neurons by inducing early cell death.
Ectopic expression of thorax-specific Hox genes Antp and Ubx also induced NSC apoptosis. However, these genes were not normally expressed in thoracic NSCs, thus allowing the cells to propagate longer. Gould is now looking for more players in the Hox-induced death pathway, including factors that induce AbdA expression. He is also interested in features of NSCs that make them sensitive to Hox-induced apoptosis, even while many other Hox-expressing cell types are spared.
Reference:
Bello, B., et al. 2003. Neuron. 37:209–219.(Preventing apoptosis (right) enables an )