Econstudentlog

Developmental Biology (II)

Below I have included some quotes from the middle chapters of the book and some links related to the topic coverage. As I already pointed out earlier, this is an excellent book on these topics.

Germ cells have three key functions: the preservation of the genetic integrity of the germline; the generation of genetic diversity; and the transmission of genetic information to the next generation. In all but the simplest animals, the cells of the germline are the only cells that can give rise to a new organism. So, unlike body cells, which eventually all die, germ cells in a sense outlive the bodies that produced them. They are, therefore, very special cells […] In order that the number of chromosomes is kept constant from generation to generation, germ cells are produced by a specialized type of cell division, called meiosis, which halves the chromosome number. Unless this reduction by meiosis occurred, the number of chromosomes would double each time the egg was fertilized. Germ cells thus contain a single copy of each chromosome and are called haploid, whereas germ-cell precursor cells and the other somatic cells of the body contain two copies and are called diploid. The halving of chromosome number at meiosis means that when egg and sperm come together at fertilization, the diploid number of chromosomes is restored. […] An important property of germ cells is that they remain pluripotent—able to give rise to all the different types of cells in the body. Nevertheless, eggs and sperm in mammals have certain genes differentially switched off during germ-cell development by a process known as genomic imprinting […] Certain genes in eggs and sperm are imprinted, so that the activity of the same gene is different depending on whether it is of maternal or paternal origin. Improper imprinting can lead to developmental abnormalities in humans. At least 80 imprinted genes have been identified in mammals, and some are involved in growth control. […] A number of developmental disorders in humans are associated with imprinted genes. Infants with Prader-Willi syndrome fail to thrive and later can become extremely obese; they also show mental retardation and mental disturbances […] Angelman syndrome results in severe motor and mental retardation. Beckwith-Wiedemann syndrome is due to a generalized disruption of imprinting on a region of chromosome 7 and leads to excessive foetal overgrowth and an increased predisposition to cancer.”

“Sperm are motile cells, typically designed for activating the egg and delivering their nucleus into the egg cytoplasm. They essentially consist of a nucleus, mitochondria to provide an energy source, and a flagellum for movement. The sperm contributes virtually nothing to the organism other than its chromosomes. In mammals, sperm mitochondria are destroyed following fertilization, and so all mitochondria in the animal are of maternal origin. […] Different organisms have different ways of ensuring fertilization by only one sperm. […] Early development is similar in both male and female mammalian embryos, with sexual differences only appearing at later stages. The development of the individual as either male or female is genetically fixed at fertilization by the chromosomal content of the egg and sperm that fuse to form the fertilized egg. […] Each sperm carries either an X or Y chromosome, while the egg has an X. The genetic sex of a mammal is thus established at the moment of conception, when the sperm introduces either an X or a Y chromosome into the egg. […] In the absence of a Y chromosome, the default development of tissues is along the female pathway. […] Unlike animals, plants do not set aside germ cells in the embryo and germ cells are only specified when a flower develops. Any meristem cell can, in principle, give rise to a germ cell of either sex, and there are no sex chromosomes. The great majority of flowering plants give rise to flowers that contain both male and female sexual organs, in which meiosis occurs. The male sexual organs are the stamens; these produce pollen, which contains the male gamete nuclei corresponding to the sperm of animals. At the centre of the flower are the female sex organs, which consist of an ovary of two carpels, which contain the ovules. Each ovule contains an egg cell.”

“The character of specialized cells such as nerve, muscle, or skin is the result of a particular pattern of gene activity that determines which proteins are synthesized. There are more than 200 clearly recognizable differentiated cell types in mammals. How these particular patterns of gene activity develop is a central question in cell differentiation. Gene expression is under a complex set of controls that include the actions of transcription factors, and chemical modification of DNA. External signals play a key role in differentiation by triggering intracellular signalling pathways that affect gene expression. […] the central feature of cell differentiation is a change in gene expression, which brings about a change in the proteins in the cells. The genes expressed in a differentiated cell include not only those for a wide range of ‘housekeeping’ proteins, such as the enzymes involved in energy metabolism, but also genes encoding cell-specific proteins that characterize a fully differentiated cell: hemoglobin in red blood cells, keratin in skin epidermal cells, and muscle-specific actin and myosin protein filaments in muscle. […] several thousand different genes are active in any given cell in the embryo at any one time, though only a small number of these may be involved in specifying cell fate or differentiation. […] Cell differentiation is known to be controlled by a wide range of external signals but it is important to remember that, while these external signals are often referred to as being ‘instructive’, they are ‘selective’, in the sense that the number of developmental options open to a cell at any given time is limited. These options are set by the cell’s internal state which, in turn, reflects its developmental history. External signals cannot, for example, convert an endodermal cell into a muscle or nerve cell. Most of the molecules that act as developmentally important signals between cells during development are proteins or peptides, and their effect is usually to induce a change in gene expression. […] The same external signals can be used again and again with different effects because the cells’ histories are different. […] At least 1,000 different transcription factors are encoded in the genomes of the fly and the nematode, and as many as 3,000 in the human genome. On average, around five different transcription factors act together at a control region […] In general, it can be assumed that activation of each gene involves a unique combination of transcription factors.”

“Stem cells involve some special features in relation to differentiation. A single stem cell can divide to produce two daughter cells, one of which remains a stem cell while the other gives rise to a lineage of differentiating cells. This occurs in our skin and gut all the time and also in the production of blood cells. It also occurs in the embryo. […] Embryonic stem (ES) cells from the inner cell mass of the early mammalian embryo when the primitive streak forms, can, in culture, differentiate into a wide variety of cell types, and have potential uses in regenerative medicine. […] it is now possible to make adult body cells into stem cells, which has important implications for regenerative medicine. […] The goal of regenerative medicine is to restore the structure and function of damaged or diseased tissues. As stem cells can proliferate and differentiate into a wide range of cell types, they are strong candidates for use in cell-replacement therapy, the restoration of tissue function by the introduction of new healthy cells. […] The generation of insulin-producing pancreatic β cells from ES cells to replace those destroyed in type 1 diabetes is a prime medical target. Treatments that direct the differentiation of ES cells towards making endoderm derivatives such as pancreatic cells have been particularly difficult to find. […] The neurodegenerative Parkinson disease is another medical target. […] To generate […] stem cells of the patient’s own tissue type would be a great advantage, and the recent development of induced pluripotent stem cells (iPS cells) offers […] exciting new opportunities. […] There is [however] risk of tumour induction in patients undergoing cell-replacement therapy with ES cells or iPS cells; undifferentiated pluripotent cells introduced into the patient could cause tumours. Only stringent selection procedures that ensure no undifferentiated cells are present in the transplanted cell population will overcome this problem. And it is not yet clear how stable differentiated ES cells and iPS cells will be in the long term.”

“In general, the success rate of cloning by body-cell nuclear transfer in mammals is low, and the reasons for this are not yet well understood. […] Most cloned mammals derived from nuclear transplantation are usually abnormal in some way. The cause of failure is incomplete reprogramming of the donor nucleus to remove all the earlier modifications. A related cause of abnormality may be that the reprogrammed genes have not gone through the normal imprinting process that occurs during germ-cell development, where different genes are silenced in the male and female parents. The abnormalities in adults that do develop from cloned embryos include early death, limb deformities and hypertension in cattle, and immune impairment in mice. All these defects are thought to be due to abnormalities of gene expression that arise from the cloning process. Studies have shown that some 5% of the genes in cloned mice are not correctly expressed and that almost half of the imprinted genes are incorrectly expressed.”

“Organ development involves large numbers of genes and, because of this complexity, general principles can be quite difficult to distinguish. Nevertheless, many of the mechanisms used in organogenesis are similar to those of earlier development, and certain signals are used again and again. Pattern formation in development in a variety of organs can be specified by position information, which is specified by a gradient in some property. […] Not surprisingly, the vascular system, including blood vessels and blood cells, is among the first organ systems to develop in vertebrate embryos, so that oxygen and nutrients can be delivered to the rapidly developing tissues. The defining cell type of the vascular system is the endothelial cell, which forms the lining of the entire circulatory system, including the heart, veins, and arteries. Blood vessels are formed by endothelial cells and these vessels are then covered by connective tissue and smooth muscle cells. Arteries and veins are defined by the direction of blood flow as well as by structural and functional differences; the cells are specified as arterial or venous before they form blood vessels but they can switch identity. […] Differentiation of the vascular cells requires the growth factor VEGF (vascular endothelial growth factor) and its receptors, and VEGF stimulates their proliferation. Expression of the Vegf gene is induced by lack of oxygen and thus an active organ using up oxygen promotes its own vascularization. New blood capillaries are formed by sprouting from pre-existing blood vessels and proliferation of cells at the tip of the sprout. […] During their development, blood vessels navigate along specific paths towards their targets […]. Many solid tumours produce VEGF and other growth factors that stimulate vascular development and so promote the tumour’s growth, and blocking new vessel formation is thus a means of reducing tumour growth. […] In humans, about 1 in 100 live-born infants has some congenital heart malformation, while in utero, heart malformation leading to death of the embryo occurs in between 5 and 10% of conceptions.”

“Separation of the digits […] is due to the programmed cell death of the cells between these digits’ cartilaginous elements. The webbed feet of ducks and other waterfowl are simply the result of less cell death between the digits. […] the death of cells between the digits is essential for separating the digits. The development of the vertebrate nervous system also involves the death of large numbers of neurons.”

Links:

Budding.
Gonad.
Down Syndrome.
Fertilization. In vitro fertilisation. Preimplantation genetic diagnosis.
SRY gene.
X-inactivation. Dosage compensation.
Cellular differentiation.
MyoD.
Signal transduction. Enhancer (genetics).
Epigenetics.
Hematopoiesis. Hematopoietic stem cell transplantation. Hemoglobin. Sickle cell anemia.
Skin. Dermis. Fibroblast. Epidermis.
Skeletal muscle. Myogenesis. Myoblast.
Cloning. Dolly.
Organogenesis.
Limb development. Limb bud. Progress zone model. Apical ectodermal ridge. Polarizing region/Zone of polarizing activity. Sonic hedgehog.
Imaginal disc. Pax6. Aniridia. Neural tube.
Branching morphogenesis.
Pistil.
ABC model of flower development.

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July 16, 2018 - Posted by | Biology, Books, Botany, Cancer/oncology, Diabetes, Genetics, Medicine, Molecular biology, Ophthalmology

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