Embryo Project Encyclopedia Articles

Regeneration is a fascinating phenomenon. The fact that many organisms have the capacity to regenerate lost parts and even remake complete copies of themselves is difficult to fathom; so difficult, in fact, that for a very long time people were reluctant to believe regeneration actually took place. It seemed unbelievable that some organisms could re-grow lost limbs, organs, and other body parts. If only we could do the same! Unfortunately, our regenerative capacities are limited to hair, nails, and skin, while the liver and a few other tissues display more restricted regenerative abilities. What if we could grow back lost limbs, or damaged organs? This question has inspired many stories, dating back to Greek mythology, wherein Prometheus was doomed to regenerate his liver after it had been devoured by birds. Regeneration has permeated many imaginations; it has appeared in many literary and religious texts, and has also provoked much interest from the scientific community.

The gradient theory is recognized as Charles Manning Child's most significant scientific contribution. Gradients brought together Child's interest in development and his fascination with the origins of individuality and organization. The gradient theory grew from his studies of regeneration, which were largely based on work he conducted with marine invertebrates, such as the ascidian flat worm, planaria and the hydroid, tubularia. Child observed that regeneration occurred in a graded process along the axis of the organism, with the characteristics of each physiological process seemingly determined by its location along the axis. To explain these observations, Child posited the existence of physiological factors working to guide the regenerative process. He was convinced that these differences along the gradients could be explained quantitatively.

Alejandro Sánchez Alvarado's laboratory group has employed molecular tools to investigate old questions about regeneration and as a result have identified some of the molecular mechanisms determining polarity. Recent work by his group has shown Wnt-β-catenin signaling determines whether a tail or a head will form during regeneration in planarians. This study was motivated by work Thomas Hunt Morgan conducted in the late nineteenth century. Morgan observed that during regeneration a planarian cut into rather small pieces would sometimes regenerate a head at both its anterior and posterior end rather than a head and a tail. This led Morgan to think the size of the piece must affect the regenerative process.

Alejandro Sánchez Alvarado is a Professor of Neurobiology and Anatomy at the University of Utah School of Medicine and is also a Howard Hughes Medical Institute Investigator. Born in Caracas, Venezuela, 24 February 1964, Sánchez Alvarado left his home to pursue education in the United States, where he received a Bachelor of Science in molecular biology and chemistry from Vanderbilt University in 1986 and a Doctorate in pharmacology and cell biophysics at the University of Cincinnati College of Medicine in 1992. During his PhD studies Sánchez Alvarado examined the in vitro differentiation of mouse embryonic stem cells. In 1994 he began a postdoctoral position at the Carnegie Institution of Washington's Department of Embryology, where he was appointed a staff associate in 1995. In 2002 he became an Associate Professor at the University of Utah School of Medicine in the Department of Neurobiology and Anatomy, and was promoted to Professor in 2005.

For Thomas Hunt Morgan clarity was of utmost importance. He was therefore frustrated with the many disparate, disconnected terms that were used to refer to similar, if not the same, regenerative processes within organisms. When Morgan wrote Regeneration in 1901 there had been many different terms developed and adopted by various investigators to describe their observations. As a result there were many inconsistencies making it difficult to discuss results comparatively and also making it more challenging to generalize. Defining terms was a priority for Morgan. He appreciated the diversity of phenomena that had been studied and sought to develop language to facilitate further studies and interpretations.

Abraham Trembley's discovery of the remarkable regenerative capacity of the hydra caused many to question their beliefs about the generation of organisms. Born 3 September 1710 to a prominent Geneva family, Trembley studied at the Calvin Institute, now the University of Geneva, where he completed his thesis on calculus. He went on to become tutor for Count William Bentinck's two sons, and it was while teaching the boys natural history that Trembley came across a strange organism in a sample of pond water. This mysterious polyp, or hydra, had been previously described by Antoni van Leeuwenhoek, as well as an anonymous English gentleman in 1704, but Trembley was unaware of the polyp's identity and began a series of experiments to determine whether it was an animal or a plant. His investigations were also motivated by his observation that the number of arms on different polyps varied, an irregularity uncommon in animals. Yet Trembley felt that it was an animal.