by Alisa Zapp Machalek
April 2, 2002

One of the most intriguing questions in human biology is how a single, fertilized egg can develop into a healthy baby. What tells some cells to form a liver, others to form bones, and still others to become blood vessels or nerves? And, even more basic, how does the developing embryo know right from left, up from down, and front from back so that all the organs are positioned properly?

Like many interesting biological questions, these are far too complex--and unethical--to answer by studying developing human embryos. So many researchers turn to simpler organisms that are genetically similar to humans. Zebrafish eggs are ideal for these studies because they are transparent, inexpensive, and hatch only 3 days after fertilization.

A team of Vanderbilt University geneticists led by Dr. Lilianna Solnica-Krezel discovered, to their surprise, that just two genes make the difference between a normal and a headless zebrafish embryo.¹ The genes, called bozozok and chordino, were known to be involved in early development. When the scientists "knocked out" these two genes, the resulting embryos developed into overgrown tails--entirely devoid of heads or trunks. The work further showed that the role of these two genes is to suppress the activity of a protein called BMP, which is required for tail formation but blocks head formation.

The study reveals a stunningly simple genetic mechanism, involving just three factors (the two genes and BMP), that is key to the complex development of a single egg into a fully developed fish. Because zebrafish have biochemical and genetic pathways similar to other vertebrates, the work will greatly advance our understanding of development in humans and other organisms. It will also shed light on the genetic basis of some serious birth defects.

REFERENCE

¹Gonzalez E, Fekany-Lee K, Carmany-Rampey A, Erter C, Topczewski J, Wright CVE, Solnica-Krezel L. Head and trunk in zebrafish arise via coinhibition of BMP signaling by bozozok and chordino. Genes & Development 14:3087-92, 2000.

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