Embryo Project Encyclopedia

"Induction and Patterning of the Primitive Streak, an Organizing Center of Gastrulation in the Amniote," (hereafter referred to as "Induction") examines the mechanisms underlying early amniote gastrulation and the formation of the primitive streak and midline axis. The review, authored by Takashi Mikawa and colleagues at Cornell University Medical College, was published in Developmental Dynamics in 2004. The article primarily discusses chick embryos as a model organism for nonrodent amniote gastrulation, although it intermittently touches on nonamniote gastrulation for comparative purposes. "Induction" attempts to explain the initiation of cell differentiation and embryo organization, one of the most intriguing processes of embryology.

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.

"A Diffusible Agent of Mouse Sarcoma, Producing Hyperplasia of Sympathetic Ganglia and Hyperneurotization of Viscera in the Chick Embryo," by Rita Levi-Montalcini and Viktor Hamburger, appeared in 1953 in the Journal of Experimental Zoology. The paper provided the first evidence that nerve growth factor is a diffusible substance. Nerve growth promoting tumors were implanted into developing embryos to determine whether the tumors stimulated growth by direct contact or by a diffusible substance. The tumors were implanted into different parts of the embryo; one set of experiments implanted the tumor directly in the embryo, while another set of experiments placed the tumor on an exterior membrane. The membrane provided a barrier to direct contact with the nervous system, and allowed some chemical interaction between the tumor and the embryo. The tumor stimulated growth in both orientations, demonstrating that nerve growth factor was a chemical agent. The paper ends with two possible conclusions for the mechanism of nerve growth, the tumor may have been directly stimulating the ganglia by a diffusible signal, or it may have reduced the resistance of the chick tissues to the nerve growth. The term "nerve growth factor" is not explicitly used in this paper, and is referred to as a "diffusible agent" or a "growth promoting agent."

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.

Nicole Marthe Le Douarin was one of the first progressive female pioneers of developmental and embryological research. Some of her most notable and ground-breaking work involves grafting quail and chicken embryos together in order to study the developmental fate of each contributing embryo. Le Douarin was born in Brittany, France, on 20 August 1930. As an only child she was inspired by her mother, a school teacher at the time, to develop a passion for learning. According to Le Douarin her father was an open-minded businessman who, likely because she was an only child, raised her much like a boy. In 1944 Le Douarin was forced to move out of her hometown of Lorient and attend a boarding school in Nantes, France, to escape the invasion of German forces during World War II. After the war, she returned to her high school in Lorient, where she received her baccalaureate in 1949. During her last year in Lorient, when she was only seventeen, Douarin met her fianc_. After graduating, and against the wishes of her mother, she moved with him to Paris where they attended the Sorbonne. In 1951, after three years of courtship and university classes together, the couple was married. Le Douarin graduated from the Sorbonne with a degree in the natural sciences in 1954. Instead of immediately continuing to graduate school, she chose to teach science at a local high school and raise a family.

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.