Zero to Birth by William A. Harris;

Author:William A. Harris; [Harris;, William A.]
Language: eng
Format: epub
ISBN: 9780691211312
Publisher: Princeton UP
Published: 2022-01-11T00:00:00+00:00

Attraction and Repulsion

In the 1980s, Andrew Lumsden and Alun Davies at University College London were asking how certain sensory axons find their way to the base of the whiskers in a mouse. Mice build up a touch-based map of their local world by whisking their whiskers, which are heavily innervated. The region of epidermis that contains the base of the whiskers, called the “maxillary pad,” is the target of many sensory axons of the fifth cranial nerve. Lumsden and Davies put these sensory neurons and the maxillary pad close to each other in a tissue culture dish at a stage preceding their contact. The axons grew directly toward the maxillary pad, and they were not fooled or diverted toward other tissues, which Lumsden and Davies sometimes added to the co-cultures. The researchers inferred that the maxillary pad releases diffusible molecules that attracts these sensory axons.13 Chemoattraction is a process in biology whereby a cell detects a local chemical gradient of a substance and then moves toward it. For example, chemoattraction helps white blood cells move to sites of infection. Because it came from the maxillary pad, Lumsden and Davies nicknamed the unknown chemoattractant “Max Factor.”

The existence of such a chemoattractant might seem to contradict the work described in the previous section, which suggested that targets do not attract incoming axons from a long distance. But because attractants in the brain tend to stick to the substratum of extracellular material soon after they are secreted, they are detected only when axons are near the sites of secretion. In addition to attractants in the local environment, cells can also secrete chemorepellents, which growth cones avoid if they get too close. Thus, while the maxillary pad is secreting chemoattractants, nearby tissues secrete chemorepellents, so there really is only one good choice for these sensory axons, which is to enter the maxillary pad and innervate the whiskers.

The 1990s heralded a new era of rapid discovery of the molecular nature of life, which followed from advances in modern molecular genetics and genetic engineering. Scientists were finding and sequencing the proteins and genes responsible for almost any process that could be tested in a culture dish or model organism, such as nematodes, flies, and mice. This work enabled searches for the molecular nature of chemoattractants and chemorepellents. In 1990, Edward Hedgecock and colleagues at the Johns Hopkins University found three genes that affected the navigation of pioneer axons in the tiny nematode, C. elegans. These genes came from a set of mutants with uncoordinated locomotion, so they all were called simply unc (uncoordinated) mutants. One of these three unc mutants affected the navigation of axons traveling dorsally, another affected the navigation of axons traveling ventrally, and yet another affected both dorsal and ventral axon navigation. Hedgecock and colleagues then cloned these genes. The one unc gene that affected both dorsal and ventral navigation turned out to encode a novel secreted protein that guides axons.14 Marc Tessier-Lavigne and colleagues at the University of California, San Francisco, soon

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