A growing nerve bears at its bow a structure called the growth cone, a region rich in the receptor molecules whose job is to receive cues from the environment, much as ancient mariners who observed the stars and set their course accordingly. During development, the growth cone continuously pushes forward, while the lengthening neuron behind it matures into the part of the cell called the axon. Once the growing cell lands at its target in a muscle cell, it is the axon that will relay the messages that allow an animal to control and move its limbs at will.
In Magellan mutants, Pfaffs team discovered that the growth cone becomes disordered. Rather than forming a distinct cap on the developing neuron, the cone is dispersed in pieces along both the forward end and the axon extending behind it.
The defect is found in the structure of the neuron itself, said Pfaff, noting that the fundamental pieces, such as the receptors capable of reading cues, all seem to be present. Without the correct orientation of receptors, however, signals cannot be read accurately, resulting in growth going off course.
A precise gradient normally exists across the cone, said Pfaff, which is disrupted in the Magellan mutants. As a result, cells lose their polarity. They literally do not know the front end from the back end, according to Pfaff. This sense of polarity is a universal feature common to all growing neurons. Therefore, Phr1 is likely to play a role in most growing neurons to ensure their structure is retained at the same time they are growing larger, he said.
Pfaff and his group identified Magellan using a novel system they had developed, in which individual motor neurons and axons can be visualized fluorescently. They were able to screen more than a quarter of a million mutations, and the mutations of interest were rapidly mapped to known genes as a result of the availability
|Contact: Gina Kirchweger|