Embryo Project Encyclopedia

Leonard Hayflick studied the processes by which cells age during the twentieth and twenty-first centuries in the United States. In 1961 at the Wistar Institute in the US, Hayflick researched a phenomenon later called the Hayflick Limit, or the claim that normal human cells can only divide forty to sixty times before they cannot divide any further. Researchers later found that the cause of the Hayflick Limit is the shortening of telomeres, or portions of DNA at the ends of chromosomes that slowly degrade as cells replicate. Hayflick used his research on normal embryonic cells to develop a vaccine for polio, and from HayflickÕs published directions, scientists developed vaccines for rubella, rabies, adenovirus, measles, chickenpox and shingles.

Leonard Hayflick in the US during the early 1960s showed that normal populations of embryonic cells divide a finite number of times. He published his results as 'The Limited In Vitro Lifetime of Human Diploid Cell Strains' in 1964. Hayflick performed the experiment with WI-38 fetal lung cells, named after the Wistar Institute, in Philadelphia, Pennsylvania, where Hayflick worked. Frank MacFarlane Burnet, later called the limit in capacity for cellular division the Hayflick Limit in 1974. In the experiment, Hayflick refuted Alexis Carrel's hypothesis that cells could be transplanted and multiplied indefinitely from a single parent cell line.

Telomeres are structures at the ends of DNA strands that get longer in the DNA of sperm cells as males age. That phenomenon is different for most other types of cells, for which telomeres get shorter as organisms age. In 1992, scientists showed that telomere length (TL) in sperm increases with age in contrast to most cell of most other types. Telomeres are the protective caps at the end of DNA strands that preserve chromosomal integrity and contribute to DNA length and stability. In most cells, telomeres shorten with each cell division due to incomplete replication, though the enzyme telomerase functions in some cell lines that undergo repetitive divisions to replenish any lost length and to prevent degradation. Cells, and therefore organisms, with short telomeres are more susceptible to mutations and genetic diseases. While TL increases in a subset of sperm cells and longer telomeres may prevent early disintegration of DNA, it may also prevent natural mechanisms of apoptosis, or cell death, from occurring in abnormal sperm.

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.

Apoptosis, or programmed cell death, is a mechanism in embryonic development that occurs naturally in organisms. Apoptosis is a different process from cell necrosis, which is uncontrolled cell death usually after infection or specific trauma. As cells rapidly proliferate during development, some of them undergo apoptosis, which is necessary for many stages in development, including neural development, reduction in egg cells (oocytes) at birth, as well as the shaping of fingers and vestigial organs in humans and other animals. Sydney Brenner, H. Robert Horvitz, and John E. Sulston received the Nobel Prize in Physiology or Medicine in 2002 for their work on the genetic regulation of organ development and programmed cell death. Research on cell lineages before and after embryonic development may lead to new ways to reduce or promote cell death, which can be important in preventing diseases such as Alzheimer's or cancer.

In the second half of the
twentieth century, scientists learned how to clone organisms in some
species of mammals. Scientists have applied somatic cell nuclear transfer to clone human and
mammalian embryos as a means to produce stem cells for laboratory
and medical use. Somatic cell nuclear transfer (SCNT) is a technology applied in cloning, stem cell
research and regenerative medicine. Somatic cells are cells that
have gone through the differentiation process and are not germ
cells. Somatic cells donate their nuclei, which scientists
transplant into eggs after removing their nucleuses (enucleated eggs).
Therefore, in SCNT, scientists replace the nucleus in an egg cell
with the nucleus from a somatic cell.

All cells that have a nucleus, including plant, animal, fungal cells, and most single-celled protists, also have mitochondria. Mitochondria are particles called organelles found outside the nucleus in a cell's cytoplasm. The main function of mitochondria is to supply energy to the cell, and therefore to the organism. The theory for how mitochondria evolved, proposed by Lynn Margulis in the twentieth century, is that they were once free-living organisms. Around two billion years ago, mitochondria took up residence inside larger cells, in a process called endosymbiosis, becoming functional parts of those cells. Within each mitochondrion is the mitochondrial DNA (mtDNA), which is different from the DNA in the cell's nucleus (nDNA). Organisms inherit their mitochondria only from their mothers via egg cells (oocytes). Mitochondria contribute to the development of oocytes, the release of the oocyte from the ovary (ovulation), the union of oocyte and sperm (fertilization), all stages of embryo formation (embryogenesis), and growth of the embryo after fertilization.

The Hayflick Limit is a concept that helps to explain the
mechanisms behind cellular aging. The concept states that a normal human
cell can only replicate and divide forty to sixty times before it
cannot divide anymore, and will break down by programmed cell death
or apoptosis. The concept of the Hayflick Limit revised Alexis
Carrel's earlier theory, which stated that cells can replicate
themselves infinitely. Leonard Hayflick developed the concept while
at the Wistar Institute in Philadelphia,
Pennsylvania, in 1965. In his 1974 book Intrinsic
Mutagenesis, Frank Macfarlane Burnet named the concept after
Hayflick. The concept of the Hayflick Limit helped scientists study
the effects of cellular aging on human populations from embryonic
development to death, including the discovery of the effects of
shortening repetitive sequences of DNA, called telomeres, on the
ends of chromosomes. Elizabeth Blackburn, Jack Szostak and Carol
Greider received the Nobel Prize in Physiology or Medicine in 2009
for their work on genetic structures related to the Hayflick
Limit.

The hedgehog signaling pathway is a mechanism that directs the development of embryonic cells in animals, from invertebrates to vertebrates. The hedgehog signaling pathway is a system of genes and gene products, mostly proteins, that convert one kind of signal into another, called transduction. In 1980, Christiane Nusslein-Volhard and Eric F. Wieschaus, at the European Molecular Biology Laboratory in Heidelberg, Germany, identified several fruit fly (Drosophila melanogaster) genes. They found that when those genes were changed or mutated, the mutated genes disrupted the normal development of fruit fly larvae. The researchers called one of the genes hedgehog (abbreviated hh). Nusslein-Volhard, Wieschaus, and Edward B. Lewis, at the California Institute of Technology in Pasadena, California, shared the 1995 Nobel Prize for Physiology or Medicine for their research on how genes control early embryonic development in fruit flies. The hedgehog signaling pathway is conserved across many animal taxa or phyla, from Drosophila to humans. The hedgehog signaling pathway controls several key components of embryonic development, stem-cell maintenance, and it influences the development of some cancers.

Edmund Beecher Wilson experimented with Amphioxus (Branchiostoma) embryos in 1892 to identify what caused their cells to differentiate into new types of cells during the process of development. Wilson shook apart the cells at early stages of embryonic development, and he observed the development of the isolated cells. He observed that in the normal development of Amphioxus, all three main types of symmetry, or cleavage patterns observed in embryos, could be found. Wilson proposed a hypothesis that reformed the Mosaic Theory associated with Wilhelm Roux in Germany. Wilson suggested that cells differentiated into other cells when influenced by physiological (dynamic) changes in the hereditary substance contained in cells, and not because of the qualitative division, or parcelling out, of the substance into daughter cells. Wilson published his results in August 1893.