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Nirenberg's lab found genes that shape the nervous system

In the late 1980s Marshall Nirenberg's laboratory discovered four new homeobox genes in fruit flies, NK-1 to NK-4, which help control nervous system development.

Marshall Nirenberg
Marshall Nirenberg · 1927–2010
Person
Marshall Nirenberg
Lived
1927–2010
Field
Biochemistry, genetics
From
American

The story

Marshall Nirenberg never stopped changing fields. After helping crack the genetic code in the 1960s, he moved into neurobiology, which he saw as the only other biological system built for processing information. Through the 1970s he studied neuroblastoma cells and the formation of synapses in the chick retina. In 1981 he showed that a molecule was spread in a gradient across the retina, supporting Roger Sperry's idea that each nerve cell carries a molecular address. But his team could not clone the gene for that molecule, and the failure pushed him towards an organism where genetics could be used as a tool: the fruit fly Drosophila melanogaster.

The timing was good. Homeobox genes, discovered by Walter Gehring's group in Basel in 1983, act as master switches that recognise DNA sequences and turn other genes on or off as an animal's body develops. In 1987 Nirenberg read a paper by Michael Levine showing a homeobox protein distributed strikingly in some neurons of the fly embryo but not others. At the time seventeen homeobox genes were known in Drosophila, and the field was booming.

Nirenberg had never worked with flies. When Yongsok Kim joined his laboratory as a postdoctoral fellow straight after earning his PhD in Korea, Nirenberg suggested they look for new homeobox genes. By comparing DNA sequences with the seventeen known genes, Kim soon found four new ones, which he named NK-1, NK-2, NK-3 and NK-4. Nirenberg set out their importance in the laboratory's annual report for 1987–88.

Nirenberg saw the genes as an experimental system for linking specific genes to the physical development of an organism. By 1992 studies of the NK-2 gene allowed his team to predict with a high degree of certainty how genetic instructions shaped part of the fly's central nervous system, and he expected that a similar strategy could explain how the human nervous system is assembled.

That expectation was well founded. After the fly genome was sequenced in 2000, researchers found that of 289 human genes linked to disease, 177 closely resembled fruit fly genes. Because homeobox genes help direct development so widely, understanding them holds promise for work on cancers, neurological diseases and metabolic and immune disorders.

Nirenberg kept working on fly embryos until his death in 2010, using digital scanning to trace how genes direct the wiring of neural networks.

Why it matters

The NK genes became an important family for understanding how genes shape the developing nervous system, in flies and in people.

About Marshall Nirenberg

NIH biochemist who in 1961 read the first word of the genetic code, UUU for phenylalanine, then led the race to decipher all of it, sharing the 1968 Nobel Prize in Medicine.

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Marshall Nirenberg
1927–2010 · Biochemistry, genetics
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