Cell death during development: who and why?

August 22, 2013

Cold Spring Harbor’s historic undergraduate research program continued this summer as 25 students from around the world joined us for 10 weeks. As co-directors of this program, Mike Schatz and I have the pleasure of seeing these students tackle challenging scientific problems and report their findings to their peers. Like last year, we were surprised both by the progress that the students made on their projects, and also by the way their scientific thinking changes over the course of the summer.

Greg Fuller from Johns Hopkins University (Photo by C. Brukin)

Gregory Fuller from Johns Hopkins University (Photo by Constance Brukin)

One project that particularly interested me this year was undertaken by Gregory Fuller, a student from Johns Hopkins who worked in the laboratory of Dr. Z. Josh Huang. Josh is one of the world’s experts on inhibitory neurons, and he has a particular interest in a class of such neurons called Chandelier Cells, named for their beautiful morphology. Like many neurons, numerous Chandelier Cells die over the course of development, mostly by a programmed cell death known as apoptosis. But Chandelier Cells are unique in that they tend to die later in development than most inhibitory neurons. Greg wondered, why do Chandelier Cells die so much later than other cells? And what will happen if their programmed cell death is delayed- will that have consequences for the circuit?

Chandelier cells proliferate in mouse cortex

Chandelier cells proliferate in mouse cortex

Greg’s project took advantage of techniques that make it possible to block cell death: specifically, he studied brains from knockout mice that lack the proteins required for apoptosis. He closely examined tissue from different parts of the cortex, with a focus on layers 2 and 6 where the Chandelier Cells proliferate. One surprising observation was that perturbing the programmed cell death in Chandelier Cells not only caused them to proliferate, but also caused the appearance of some small cells that didn’t look much like Chandelier cells at all. Greg’s project is still at an early stage, but his observations are intriguing. Might the small cells be Chandelier cells that didn’t develop properly? Or are they a different class of neuron that was only made apparent through Greg’s manipulation? More work is necessary to get to the bottom, but the implications could be profound. Chandelier Cells likely play a key role in shaping cortical activity, and understanding how they are integrated into circuits during development may provide major insights into how they accomplish this.

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