Consequences of the Discoveries

The Nobel Prize in Physiology or Medicine 1995

Consequences of the Discoveries

The Primitive Brain

Segmentation of the back part of the primitive brain is visible in the nine rhombomeres. The HOX-B 2 gene is expressed in rhombomere 4, the HOX-B 3 gene in rhombomeres 5 and 6 and the HOX-B 4 gene in rhombomeres 7 and 8.

Razor-sharp Boundaries

The blue color reveals the specific activity of two homeotic genes in mouse embryos. In figure A the HOX-D 2 gene is active earlier and nearer the embryo's head-end than the HOX-D 4 gene shown in figure B. In both cases there is a razor-sharp boundary at the upper end of the segment wheras gene activity is more diffuse further down.

If a HOX gene is lost the result is incorrect development of the rhombomeres concerned and - as a consequence of this - incorrect development of the branchial arches, neck or head structures.

Normal mouse embryo

Retinoic acid:
loss of many vertebrae

More retinoic acid:
no posterior region formed

Congenital Malformations in Mouse and Man

Most of the genes studied by Nüsslein-Volhard, Wieschaus and Lewis have important functions during the early development of the vertebrate embryo. Mutations in such important genes - or altering their expression patterns - may damage the embryonic development.

Two of the three mouse embryos (see above) show malformations caused by high doses of vitamin A (retinoic acid), which was given to their mothers on day 8 of pregnancy. Vitamin A has caused the homeotic HOX genes 1-4 to become expressed in groups of cells that usually do not express these genes. It is well known that high doses of vitamin A taken by women early during pregnancy can disturb the regulation of HOX genes even in the human embryo and cause severe malformations.

Waardenburg's Syndrome

Mutations have been found in human genes related to those described for Drosophila. A defective human HOX gene related to the Drosophila gene paired will cause a condition known as Waardenburg's syndrome. It is a very rare disease, affecting one of 42 000 born children. It involves deafness, defects in the facial skeleton and altered pigmentation of the iris.

The Human Embryo

The Human Embryo is, in its early stages, hard to distinguish from the embryo of a mouse, a rabbit or a giraffe. The human embryo is in fact segmented like the fruit fly larva according to a basic plan valid for all living things. The segments of the human embryo consist of somites, cell masses which develop into ribs, vertebrae and back muscles.

Aniridia

Aniridia, loss of the iris of the eye, seems to be caused by a defect in the homeotic gene PAX 6. It is a rare congenital disease.

Contents:
Introduction » Nüsslein-Volhard's and Wieschaus' Discoveries » Hunting for the Genes Behind Pattern Formation in Drosophila's Early Embryonic Development » Lewis' Discoveries » Homeotic Genes Determine Specialization of Segments » Homeotic Gene Complexes are Similar in Flies and Mammals » Consequences of the Discoveries » Aniridia » Congenital Malformations » From Egg to Adult Fly »
These pages are based on material from the 1995 Physiology or Medicine Nobel Poster. Credits and references for the poster »