What Happens In the Process of Regeneration?

Invertebrate: The process of regeneration is similar to the process of embryonic development. Undifferentiated embryonic cells are retained i.e. blastema. These cells are responsible for the formation of the missing part.


Vertebrates: Near the cut surface of amputation or injury, cells revert to an essentially embryonic state by losing their structural and functional specialization in a process called differentiation. These cells become part of blastema. Division and re-growing continues as long as needed to replace the lost parts.

Regeneration

During lifetime of an organism, some of its part may be damaged or lost. Most organisms have, to some degree, the ability to replace defective or missing parts. So the process of replacement of lost or damaged organ is called regeneration.

Regeneration In Animals
The property of regeneration is seen in variety of animals. Both invertebrates and vertebrates possess this ability.

Invertebrates
Sponges: Sponges can regenerate the entire organism from just a conglomeration (collection of things) of their cells.
Hydra: Hydra has also the same ability like sponges. 

Regeneration In Planarian 


When a Planarian worm is cut in half, regeneration begins at each cut surface with formation of blastema, where cell division and differentiation continues until an adequate population of replacement cells is produced. As a result two normal worms are formed from the one worm.

Earthworm: The earthworm can regenerate the first four or five segment of its head and even longer section of its tail. If one of its large pincers claws is lost, the lost one begins to grow. If one or more arms of the sea star are removed, new ones are formed.

Vertebrates
Among the vertebrate animals, the greatest regenerative capacity discovered so far is that of tailed amphibians such as newts and salamander, by which entire limbs can be regenerated, when they are lost.

An adult frog do not show any ability of regeneration. It is only the larvae that have regenerative ability of lost limbs.

Most of the lizards can regenerate their tail but not their limbs. They cannot regenerate entire organs, they can however, regenerate tissues and thus, repair damaged or missing parts.

The healing of skin wounds, bone, blood replacement are examples of regeneration in humans, Tongue, liver, pancreas are capable of extensive regeneration after damage.

What is Aging?

Normal cells of all complex eukaryotes have limits on their life span prescribed limits characteristics of their species. After growth and differentiation, these cells begin to deteriorate. There is a gradual loss of efficiency in cellular functions, which terminates sooner or later in the death of the individual. The over all process of predictable cellular deterioration is called aging. It can be defined as negative physiological change in our body.

Gerontology
It is the branch of biology that deals with the study of aging.

Aging in Population
Each species has its own characteristic, genetically determined range of life spans. Expected life span vary among individuals in a species, but each species has its approximate maximum expected life span.

Functional aging change
With advance age, many functional and structural features of organisms show signs of lost or decreased function. These changes, singly and in various interactive combinations, weaken an organism's homeostatic responses. Specific immune resistance mechanisms also decline with age so that organisms become more susceptible to infection.

Cellular Aging
Tissues without significant cell turnover and replacement, lose cells with aging. The nervous system for example, suffers a progressive loss in cell number throughout life. Several possible cause of cell death during aging have been suggested. For instance, certain metabolic wastes, known as aging pigments, accumulates in aging cells rather than being released, and their accumulation may eventually lead to cell death.

The accumulation of DNA, damaged due to somatic mutation, can cause disturbances in cell function if it leads to synthesis of faulty enzyme molecules that are less efficient catalysts of cellular reactions; Also, the potential for cell division may be limited in aging tissues that undergo cell replacement throughout life.

Extra-Cellular Aging
Collagen fibers, which are important permanent components of tissue because they form an extra-cellular frame work around tissue cells, show significant aging change. The collagen fibers become less elastic, thereby changing physical structure of the tissue, causing skin to become wrinkled with age.

Abnormal Aging
For most people, aging is a slow process that gradually reduces certain functional capabilities and eventually weakens resistance to various health problems. Some people, however, suffer dramatic aging changes, e.g. due to degenerative brain disorder disease.

Conclusion

Aging and death make room in populations for new, young individuals. From an evolutionary point of view, aging and death are necessary for the welfare and survival of our species and yet, the prospect of extended life span is very attractive for individuals.

Genes in Development

Gametes unite to form the zygote. The zygote has all the genetic information for the formation of different parts of an individual. The zygote divides to form the embryo. The embryo develops as per the genetic information into an organism. The organism has different types of cells and tissues.

Each cell and tissue has different functions e.g. muscle cells have protein, actin and myosin for muscle contraction, the goblet cells produce mucous and oxyntic cells produce HCl. So different cells function in different ways having the same genetic material as it was present in zygote. The question is that, how the same genetic material function differently in different types of cells?

Evidence has suggested that there are three factors, which act together in various ways to bring out differentiation. These are:

a) Nuclei
Acetabularia
b) Cytoplasm
c) Environment

The Role Of The Nucleus

Danish biologist Joachim Hammerling performed experiment on Acetabularia in 1943. It is a single celled marine green alga. Individuals have distinct foot stalk and cap regions. The nucleus of this cell is located in the foot. It grows to a length of 6 to 9 centimeter.

Hammerling selected individuals from two species of the genus in which caps looked very different from each other. Acetabularia mediterranea, which has a disk shaped cap and Acetabularia crenulata which has a branched flower like cap.

Experiment: The cap was removed from one species and thrown away. Next, the cytoplasmic stalk was cut off and grafted to the base of other species, whose stalk and cap had already been cut off and thrown away. A whole new alga grew from the joined pieces. The new organism becomes complete with cap, stalk and foot.

Acetabularia Grafting Experiment

Result: The first cap regenerated may be intermediate in type, but when it was removed, the next cap formed always had the characteristic of the species supplying the nucleus.

Conclusion: The nucleus of each grafted algal cell must exert its influence through the alien cytoplasm in determining the form of cap, so there is an evidence of nuclear control of the development processes forming a new cap.

Nuclear Equivalence
1. Spemann placed minute ligatures of human hair around salamander zygotes just as they were about to divide, constricting them until they were almost, but not quite, separated into two halves. The nucleus lay in one half of the partially divided egg, the other side was anucleate, containing only cytoplasm. The egg then completed its first cleavage division on the side containing the nucleus, the anucleated side remained undivided. Eventually, when the nucleate side had divided into about sixteen cells, one of the cleavage nuclei would wander across the narrow cytoplasmic bridge to the anucleate side. Immediately this side began to divide.

Spemann's delayed nucleation experiments

Tow kinds of experiments were performed.

(A) Hair ligature was used to constrict an uncleaved fertilized new egg. Both sides contained part of the gray crescent. The nucleated side alone cleaved until a descendant nucleus crossed the cytoplasmic bridge. Then both sides completed cleavage and formed to complete embryos.

(B) Hair ligature was placed so that the nucleus and gray crescent were completely separated. The side lacking the grey crescent became an unorganized piece of belly tissue, the other side developed normally. 

Cytoplasmic Influence On Development

(A) A frog's egg has anterior/posterior and dorsal/ventral axes that correlate with the position of the gray crescent.

(B) The first cleavage normally divides the gray crescent in half, and each daughter cell is capable of developing into a complete tadpole.

(C) But if only one daughter cell receives the gray crescent, then only that cell can become a complete embryo. This shows that the chemical messengers are not uniformly distributed in the cytoplasm of frog's eggs.

Cytoplasmic influence on development

(A) A frog's egg has anterior/posterior and dorsal/ventral axes that correlate with the position of the gray crescent.

(B) The first cleavage normally divides the gray crescent in half, and each daughter cell is capable of developing into a complete tadpole.

(C) But if only one daughter cell receives the gray crescent, then only that cell can become a complete embryo. This shows that the chemical messengers are not uniformly distributed in the cytoplasm of frog's eggs.

2. Spemann performed another experiment. He separated the two halves of embryo, both of them contained nuclei. Both these halves developed into complete embryos. He also observed that from a 16-cell embryo, even if a single cell is separated, it contains a complete set of genes and form a complete embryo cell and thus, the nuclei were equivalent.

Spemann also observed that sometimes it may happen that the nucleated half can develop into abnormal ball of cells. Later studies proved that development depend on gray crescent. Gray crescent is the pigment free area that appears at the time of fertilization. So in the half lacking gray crescent, no further development can take place.

Influence Of Cytoplasm On Nucleus During Development

Experiment No. 1: If the early embryos of Sea urchin are placed in sea water from which the calcium ions have been removed, the cells tend to separate. Thus, it is possible to isolate the two cells formed by the first cleavage or the four cells formed by the second cleavage. Each of the cell continues to develop and becomes in time, a small but complete sea urchin larva. This experiment was perfumed in 1892 by Hans Dietrich.
Influence Of Cytoplasm On Nucleus During Development

Experiment No. 2: Instead of dividing a sea urchin egg along the natural planes of cell division, we cut across the axis of an unfertilized egg. Now, we have two halves of an egg, sometimes the nucleus is located in the upper half and sometimes in the lower half.

Both the halves heal. Each forming an apparently normal cell. Then we see sea urchin sperms. A sperm will enter each half of the egg cell. If the half has a nucleus, the half will be diploid. If the half is without nucleus, then it will have only the monoploid number of chromosomes contributed by the sperm. Both the upper halves develop into a hollow ball of cells with many cilia, but it forms no internal tissues. It swims around for several days and then dies. The lower half too is very abnormal and incomplete and dies before long. Neither of the half embryos is then able to develop into a normal embryo, or even to survive for long.

Conclusion: In the experiment all the four or two cells are getting same type of nucleus so all the cells fertilized developed into embryo. In the second experiment there is different cytoplasm in the lower and upper cut cells as the cytoplasm is lacking some of the material, so after fertilization the embryos did not develop completely. This, it can be concluded that the materials indeed affect and limit what genes in the nucleus are above to do in controlling the path of the development. 





The Analysis of Development

The zygote gives rise to an adult animal. The adult can response to stimuli and can perform physiological functions. Now the question arises: How the zygote is transformed into an adult. Moreover, what makes the adult perform all types of functions?

Development by Pre-Formation or Epigenesis
Aristotle proposed two different hypotheses to account for development:
(1) Pre-Formation (2) Epigenesis

Pre-Formation
Pre-formation implies that an egg or sperm actually contains the new individual already formed.
                            
Epigenesis
According to this idea, the egg or the sperm contains no structures; rather these structures somehow develop in their proper position later, constructed from material in the egg. The development depends on the action of genes, received by the embryo from the parents, in the sense one can say that the embryo is preformed. The organization of the embryo arises by epigenesis, a process controlled by genes.

The Problem of Differentiation
If the organization of the embryo arises by epigenesis, then how the dividing cells of the zygote is differentiated into three embryonic layers? Moreover, how from these layers different structures are formed? Hans Spemann and Hilde Mangol (1924) performed a series of experiments on differentiation.

Experiment No: 1
From an amphibian embryo, they cut out the ectoderm that normal becomes the nerve tube and put the piece of ectoderm in a separate dish. an embryo from which the piece was taken healed and lived, but t had either a defective nervous system or none at all. Moreover, the isolated piece of ectoderm did not form a nervous system, though it remained alive and healthy.

Conclusion: They concluded that the piece of ectoderm should remain attached to the embryo for the proper development of nervous system. So they performed another experiment.

Experiment No: 2
They cut a flap of ectoderm from the top of an embryo. They did not remove the piece of ectoderm, but just folded it back. Then they cut out the mesoderm underneath and discarded it. Finally they folded the flap of ectoderm back in its place. The ectoderm healed and looked quite healthy, but it did not develop into a nervous system. 

Conclusion: When the mesoderm is removed, the ectoderm does not differentiate into nerve tissue. The mesoderm must influence the ectoderm somehow to differentiate into nerve tissues. So they performed another experiment.

Experiment No: 3
They used two embryos, both in the early gastrula stages, from one they removed a piece of mesoderm immediately in front of the dorsal lip of the blastopore. from the second embryo, they removed the similar size piece from the mesoderm area 180 degree from the dorsal lip i.e. exactly opposite to the dorsal lip. In its place they put the piece of mesoderm from the first embryo. The transplanted mesoderm formed as blastopore and moved inside the embryo. Two nervous systems were formed, one in front of the embryo's original dorsal lip and another in the area where transplantation was made. Thus, sort of Siamese-twin embryo was produced, having two brains and spinal cord.

Conclusion: This experiment proves that mesoderm seems to control the differentiation of nervous tissue.

Spemann designated the dorsal lip area, the primary organizer because it was the only tissue capable of inducing the development of a secondary embryo in the host. He also termed this inductive event primary induction because he believed it to be the first inductive event in development. Spemann was awarded Nobel Prize in 1935 for his experiments.

Embryonic Induction
Embryonic induction means that the cells of one kind direct the development of other cells e.g. in the experiment of Spemann mesodermal cells of the dorsal lips regions induced the ectoderm to form a nerve tube.

The Problem Of Cell Differentiation
Some parts of the genetic information are used practically by all cells because some "house keeping" activities such  as cell respiration and protein synthesis are carried out by all cells. Genetic information necessary for these processes must be expressed in all cells. But how do cells become structurally and functionally specialized for the division of labor that occurs in complex, multicellular organisms?

Each kind of specialized cell has its own particular set of special structural protein and enzyme systems. Thus, cell differentiation depends upon production of different of different sets of specific proteins by different group of cells. cells must actively express specific parts of their total store of genetic information (genome) while other parts are kept inactive (repressed). Example: Some portions of genome are used to produce one type of specialized cells e.g.  brain cells, while different portions of the genome are used to produce another type of specialized cells e.g. kidney cells.