Embryo Project Encyclopedia Articles

In 2012, a team of scientists across the US conducted an experiment to find the mechanism that allowed a group of flatworms, planarians, to regenerate any body part. The group included Danielle Wenemoser, Sylvain Lapan, Alex Wilkinson, George Bell, and Peter Reddien. They aimed to identify genes that are expressed by planarians in response to wounds that initiated a regenerative mechanism. The researchers determined several genes as important for tissue regeneration. The investigation helped scientists explain how regeneration is initiated and describe the overall regenerative mechanism of whole organisms.

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.

Edward Donnall Thomas, an American physician and scientist, gained recognition in the scientific community for conducting the first bone marrow transplant, a pioneering form of hematopoietic stem cell transplantation (HSCT). Bone marrow transplants are considered to be the first successful example of tissue engineering, a field within regenerative medicine that uses hematopoietic stem cells (HSCs) as a vehicle for treatment. Prior to Thomas's groundbreaking work, most blood-borne diseases, including certain inherited and autoimmune diseases, were considered lethal.

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.

In the early 2000s, Manjong Han, Xiaodang Yang, Jennifer Farrington, and Ken Muneoka investigated how genes and proteins in fetal mice (Mus musculus) influenced those fetal mice to regenerate severed toes at Tulane University in New Orleans, Louisiana. The group used hind limbs from mice to show how the gene Msx1 (Homeobox 7) functions in regenerating amputated digits. The researchers showed that in the process of regenerating digit tips, Msx1 genes make products that regulate or influence other genes, such as the Bone Morphogenetic Protein 4 gene (BMP4 gene), to produce proteins, such as the BMP4 proteins. The researchers also showed that BMP4 proteins, which are produced from the BMP4 gene, function in tissues during the process of limb development. Furthermore, while Msx1 genes regulate other genes during the process of regeneration, they don't produce proteins otherwise needed to organize cells in the regeneration of digit tissues. The group published their results in 2003 as Digit Regeneration Is Regulated by Msx1 and BMP4 in Fetal Mice.

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.

Tissue engineering is a field of regenerative medicine that integrates the knowledge of scientists, physicians, and engineers into the construction or reconstruction of human tissue. Practitioners of tissue engineering seek to repair, replace, maintain, and enhance the abilities of a specific tissue or organ by means of living cells. More often than not stem cells are the form of living cells used in this technology. Tissue engineering is one of the disciplines involved in translating knowledge of developmental biology into the clinical setting. One focus that this field has taken is the understanding of tissue and organ development during embryogenesis, as this knowledge will open avenues to new applications of this technology.

Induced pluripotent stem cells (iPSCs) are studied carefully by scientists not just because they are a potential source of stem cells that circumvents ethical controversy involved with experimentation on human embryos, but also because of their unique potential to advance the field of regenerative medicine. First generated in a lab by Kazutoshi Takahashi and Shinya Yamanaka in 2006, iPSCs have the ability to differentiate into cells of all types. If scientists discover how to induce differentiated cells to return to a pluripotent state using a method that leaves the iPSCs safe for transplantation, then patients could receive stem cell transplants with cells containing their own DNA. This would presumably remove the danger of transplant rejection that comes with foreign cell transplantation.

Induced Pluripotent Stem Cells (iPSCs) are cells derived from non-pluripotent cells, such as adult somatic cells, that are genetically manipulated so as to return to an undifferentiated, pluripotent state. Research on iPSCs, initiated by Shinya Yamanaka in 2006 and extended by James Thompson in 2007, has so far revealed the same properties as embryonic stem cells (ESCs), making their discovery potentially very beneficial for scientists and ethicists alike. By avoiding the destruction of embryos and the complicated technique and resource requirements of ESCs, iPSCs may prove more practical and attractive than ESC research in the study of pluripotent stem cells.

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.