Serendipity and the Siamese cat: the discovery that genes for coat and eye pigment affect the brain.

One day in the late 1960s, Ray Guillery was examining brain sections through the visual thalamus of cats, and he recognized that the arrangement of layers in the lateral geniculate nucleus (LGN) of one cat was strangely abnormal. The cat was identified as a Siamese cat, one of a breed selected for its unusual coat color, with reduced pigment over much of the body and eyes. This chance observation and the recognition of its significance led to a broad-ranging series of investigations. These experiments showed that the lack of normal levels of pigment in the retina in Siamese cats (and other hypopigmented mammals) was the critical factor in the misdirection of many of the projections of the retina to the brain, the nature of the projection error, and the developmental consequences of the relay of the misdirected retinal inputs to visual cortex. As a result, we have a better understanding of how the brain forms proper connections and of the neural basis of visual problems in albino humans.