Many inhibitory cells come from a large incubator area called the MGE (medial ganglionic eminence); until now, it was not known that most chandelier cells are not born there, and indeed do not emerge until after the MGE has disappeared. Only at this point does the much smaller VGZ form, providing a place where neural precursor cells specifically give rise to chandelier cells.
The team learned that manufacture of a protein encoded by a gene called Nkx2.1 is among the signals marking the birth of a chandelier cell. The gene's action, they found, is also necessary to make the cells. Nkx2.1is a transcription factor, whose expression has previously been linked to the birth of other inhibitory neuronal types. Huang's team observes that it is the timing of Nkx2.1's expression in certain precursors -- following disappearance of the MGE and appearance of the VGZ -- that enabled them to track the birth, specifically, of chandelier cells.
Highly specific migration route and cortical destinations
"In addition to being surprised to discover that chandelier cells are born 'late'after other inhibitory cells in a part of the cortex we didn't know about," says Huang, "our second surprise is that once born, these cells take a very stereotyped route into the cortex and assume very specific positions, in three cortical layers." (Layers 2, 5 and 6). "This leads us to postulate that other specific cortical cell types also have specific migration routes in development."
As Huang points out, his team's new discoveries about chandelier cells have implications for disease research, since it is known that the number and connective density of chandelier cells is diminished in schizophrenia. Associations of the same type have recently been made in epilepsy.
"To know the identity of a cell type in the cortex is in effect to know the intrinsic program that di
|Contact: Peter Tarr|
Cold Spring Harbor Laboratory