Organizing principles

© Images courtesy of The International Journal of Developmental Biology, UBC Press, Spain.

A central question in developmental biology is how form and pattern emerge from the simple beginnings of a fertilized egg. How and when do individual cells and tissues decide which developmental route to take? Are cell fates somehow predetermined or do cells and tissues interact with one another to orchestrate developmental processes?

A groundbreaking (and technically demanding) experiment published in 1924 recognized one fundamental principle during development: embryonic induction. It provided the first unambiguous evidence that cell and tissue fate can be determined by signals received from other cells. This experiment, probably the best known in embryology, was carried out by Hilde Mangold, a Ph.D. student in the laboratory of Hans Spemann in Freiburg.

The experiment was performed in newt embryos at the gastrulation stage, the period during which the three primary germ layers — ectoderm, mesoderm and endoderm — are established. It involved transplantation of a structure on the dorsal side of the blastopore embryo, called the dorsal lip, to the ventral side of another embryo. By grafting tissue between differently pigmented Triton species, the fates of the graft and host tissues could be distinguished. This graft, nowadays referred to as the Spemann organizer (also the Spemann–Mangold organizer) had two effects. It induced the formation of neural tissues from ectoderm that would have otherwise assumed an epidermal fate (neuralization), and it caused dorsalization of the ventral mesoderm, leading to the formation of somites. This resulted in the formation of a second embryonic axis, and therefore a twin embryo, at the graft site. Importantly, all of these structures were composed of both graft and host cells.

This experiment therefore demonstrated the existence of an organizer that instructs both neuralization and dorsalization, and showed that cells can adopt their developmental fate according to their position when instructed by other cells.

	In my opinion this is probably the single most influential research paper to have been published in the field of developmental biology.   Ivor Mason

The molecular nature of this signal remained elusive until 65 years later (see also Milestone 19), and it is still not completely understood. In contrast to expectations, for example, the signal released by the organizer to cause dorsalization turned out not to be a direct inducer, but instead consisted of antagonists, which block other inhibitors that are present throughout the mesoderm and that prevent the dorsalization of adjacent tissue.

Hans Spemann was awarded the Nobel Prize in 1935 for his work on embryonic induction. Hilde Mangold tragically died in a house fire at the age of 26, even before the paper was published in 1924. Today, we know that their discovery of signals from one cell or tissue instructing the fate of others is a widely used principle in development.