The fine art of brain development  pg. 5

“It was kind of puzzling that we found a putative transcription factor 'out there' at the cell surface of the neuron (instead of in the nucleus),” Carter said.

Cross-section through the midbrain of a 4-day-old zebrafish larva. Axons coming from both sides of the forebrain have been labeled with green fluorescent protein, while only those coming from the left have been tagged, in red, with an antibody. Cell nuclei have been stained blue.
Epifluorescence microscopy image by Robert Taylor, graduate student in the Vanderbilt Department of Biological Sciences, courtesy of Josh Gamse, Ph.D.
Carter and research instructor Rajappa Kenchappa, Ph.D., have since determined that an enzyme cleaves p75, liberating NRIF from the cell surface and allowing it to travel to the nucleus to affect its “pro-death” signal.

This mechanism may explain some of the naturally occurring neuron death during development. Mice lacking p75 have an overabundance of neurons because the cells cannot die, Carter says.

Knowing these 'death signals' could also allow researchers to develop therapies that prevent the undesirable cell death that occurs in neurodegenerative diseases like Alzheimer's as well as after spinal cord injury and stroke.

Structure vs. function

It’s not enough just to have the appropriate complement of neurons; they must also connect with other neurons. The formation of these connections, or synapses, sets up communication links between neurons. The ability to alter the strength and number of these connections—a property known as “plasticity”—throughout the entire lifespan of an organism drives behavioral changes and underlies learning.

“Synapse formation … is the end of building structure and the beginning of building function,” Broadie says.

In humans, synapse formation begins during late embryonic development (around the beginning of the third trimester) after the bulk of brain “building” is complete. And, unlike the earlier steps of brain development—differentiation, migration and axon guidance to their targets—synapse formation and later plasticity are dependent on neural activity, particularly on sensory activity.

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