A puzzle piece found in unraveling the wiring of the brain

The complexity of the brain and, more specifically, how nerve cells form billions of contacts when there are fewer than 30,000 human genes is still a scientific mystery.

A team headed by Drs. Robin Hiesinger and Hugo J. Bellen at Baylor College of Medicine in Houston have unraveled a piece of that puzzle by finding a gene that plays a key role in brain wiring. A report on their work appears today in the journal Neuron.

“We were surprised to find an exocyst mutant having such specific defects,” said Bellen, professor of molecular and human genetics at BCM. “The cell biological basis of brain wiring is largely unknown. We are happy to have a new handle on an old problem.”

Using sophisticated genetics applied to the brain of the fruit fly, Drs. Sunil Mehta and Hiesinger found a gene named sec15 that is required for nerve cells to make appropriate choices of targets on which to act.

The Sec15 protein is part of a protein complex (the exocyst) which is known to be required for secretion (or exocytosis) of vesicular compartments in yeast. Vesicular compartments are small organelles that transport proteins from one site to another in the cell.

Neurons in the fly brain that lack sec15 not only display aberrant wiring patterns, but also show misplacement of proteins required for correct nerve cell contact choices.

Most of these cell contact proteins were previously known to display highly dynamic expression patterns in both time and space, but how they are put at the right time and at the right place remains to be shown. This study answers part of that question.

Others who participated in this work include Dr. Mike Crair of BCM, Drs. R. Grace Zhai, Karen L. Schulze, Patrik Verstreken, Yu Cao and Yi Zhou from the Howard Hughes Medical Institute at BCM and Drs. Slobodan Beronja and Ulrich Tepass from the University of Toronto.