Cell polarity refers to spatial differences in shape and function within a cell. All cell types exhibit some form of polarity, which enables them to carry out specialized functions. Classical examples of polarized cells are described below, including epithelial cells with apical-basal polarity, neurons in which signals propagate in one direction from dendrites to axons, migrating cells. Furthermore, cell polarity is important during many types of asymmetric cell division to set up functional asymmetries between daughter cells. Many of the key molecular players implicated in cell polarity are well conserved. For example, in metazoan cells, the PAR-3/PAR-6/aPKC complex plays a fundamental role in cell polarity. While the biochemical details may vary, some of the core principles such as negative and/or positive feedback between different molecules are common and essential to many known polarity systems. Epithelial cells adhere to one another through tight junctions and adherens junctions, forming sheets of cells that line the surface of the animal body and internal cavities.
These cells have an apical-basal polarity defined by the apical membrane facing the outside surface of the body, or the lumen of internal cavities, the basolateral membrane oriented away from the lumen. The basolateral membrane refers to both the lateral membrane where cell-cell junctions connect neighboring cells and to the basal membrane where cells are attached to the basement membrane, a thin sheet of extracellular matrix proteins that separates the epithelial sheet from underlying cells and connective tissue. Epithelial cells exhibit planar cell polarity, in which specialized structures are orientated within the plane of the epithelial sheet; some examples of planar cell polarity include the scales of fish being oriented in the same direction and the feathers of birds, the fur of mammals, the cuticular projections on the bodies and appendages of flies and other insects. A neuron receives signals from neighboring cells through branched, cellular extensions called dendrites; the neuron propagates an electrical signal down a specialized axon extension to the synapse, where neurotransmitters are released to propagate the signal to another neuron or effector cell.
The polarity of the neuron thus facilitates the directional flow of information, required for communication between neurons and effector cells. Many cell types are capable of migration, such as leukocytes and fibroblasts, in order for these cells to move in one direction, they must have a defined front and rear. At the front of the cell is the leading edge, defined by a flat ruffling of the cell membrane called the lamellipodium or thin protrusions called filopodia. Here, actin polymerization in the direction of migration allows cells to extend the leading edge of the cell and to attach to the surface. At the rear of the cell, adhesions are disassembled and bundles of actin microfilaments, called stress fibers and pull the trailing edge forward to keep up with the rest of the cell. Without this front-rear polarity, cells would be unable to coordinate directed migration. Main article: Polarity establishment in yeast Generation of cellular polarity is critically important for the function of every cell type and underlies processes like cell division, cell migration, cell–cell signalling and fertilization.
Cell polarity is an example of the self-organization property. All the cells within a multicellular organism, or any single cell species i.e. yeast, displays a polarized organization necessary for its proliferation, differentiation or physiological function. Budding yeast is a accessible experimental system, which serves as a paradigm for deciphering the molecular mechanism underlying the generation of polarity. Yeast cells share many features about cell polarity with other organism like: regulation by intrinsic and extrinsic cues, conserved regulatory molecules such as Cdc42GTPase, asymmetry of the cytoskeleton. Cell polarization is associated with a type of symmetry breaking, that occurs in the cytoskeleton and guides the direction of growth of the future daughter cell; this symmetry breaking facilitates the polarized flux and localization of several protein in the polarized patch. When cells can perform symmetry breaking in absence of any spatial cue, is called spontaneous polarization or spontaneous symmetry breaking.
In short, polarity establishment or symmetry breaking, in this context, is the first step for cell polarity and cell division. We are interested in the spontaneous symmetry breaking, as an example of self-organization phenomena in living cells. One of the way, one of the most popular ones, to study spontaneous symmetry breaking is by correlating it with a type of reaction- diffusion phenomena; the molecular identity of most important proteins involved in leading spontaneous symmetry breaking have been extensively studied. Those proteins have been categorized in general modules that represent the main functional cores for yeast life cycle. However, the molecular mechanisms responsible for this regulatory network are still poorly understood. Extensive work done in many organisms ranging from prokaryotes to high complex ones has revealed a central role of small GTPases in the cell polarization process. In yeast, this protein is Cdc42, a member of the eukaryotic Ras-homologous Rho-family of GTPases, part of the wider super-family of small GTPases, including Rop GTPases in plants and small GTPases in prokaryotes.
A recent study to elucidate the connection between cell cycle timing and Cdc42 accumulation in the bud site uses o
Transcription is the first step of gene expression, in which a particular segment of DNA is copied into RNA by the enzyme RNA polymerase. Both DNA and RNA are nucleic acids. During transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. Transcription proceeds in the following general steps: RNA polymerase, together with one or more general transcription factors, binds to promoter DNA. RNA polymerase creates a transcription bubble; this is done by breaking the hydrogen bonds between complementary DNA nucleotides. RNA polymerase adds RNA nucleotides. RNA sugar-phosphate backbone forms with assistance from RNA polymerase to form an RNA strand. Hydrogen bonds of the RNA–DNA helix break, freeing the newly synthesized RNA strand. If the cell has a nucleus, the RNA may be further processed; this may include polyadenylation and splicing. The RNA may exit to the cytoplasm through the nuclear pore complex; the stretch of DNA transcribed into an RNA molecule is called a transcription unit and encodes at least one gene.
If the gene encodes a protein, the transcription produces messenger RNA. Alternatively, the transcribed gene may encode for non-coding RNA such as microRNA, ribosomal RNA, transfer RNA, or enzymatic RNA molecules called ribozymes. Overall, RNA helps synthesize and process proteins. In virology, the term may be used when referring to mRNA synthesis from an RNA molecule. For instance, the genome of a negative-sense single-stranded RNA virus may be template for a positive-sense single-stranded RNA; this is because the positive-sense strand contains the information needed to translate the viral proteins for viral replication afterwards. This process is catalyzed by a viral RNA replicase. A DNA transcription unit encoding for a protein may contain both a coding sequence, which will be translated into the protein, regulatory sequences, which direct and regulate the synthesis of that protein; the regulatory sequence before the coding sequence is called the five prime untranslated region. As opposed to DNA replication, transcription results in an RNA complement that includes the nucleotide uracil in all instances where thymine would have occurred in a DNA complement.
Only one of the two DNA strands serve as a template for transcription. The antisense strand of DNA is read by RNA polymerase from the 3' end to the 5' end during transcription; the complementary RNA is created in the opposite direction, in the 5' → 3' direction, matching the sequence of the sense strand with the exception of switching uracil for thymine. This directionality is because RNA polymerase can only add nucleotides to the 3' end of the growing mRNA chain; this use of only the 3' → 5' DNA strand eliminates the need for the Okazaki fragments that are seen in DNA replication. This removes the need for an RNA primer to initiate RNA synthesis, as is the case in DNA replication; the non-template strand of DNA is called the coding strand, because its sequence is the same as the newly created RNA transcript. This is the strand, used by convention when presenting a DNA sequence. Transcription has some proofreading mechanisms, but they are fewer and less effective than the controls for copying DNA.
As a result, transcription has a lower copying fidelity than DNA replication. Transcription is divided into initiation, promoter escape and termination. Transcription begins with the binding of RNA polymerase, together with one or more general transcription factors, to a specific DNA sequence referred to as a "promoter" to form an RNA polymerase-promoter "closed complex". In the "closed complex" the promoter DNA is still double-stranded. RNA polymerase, assisted by one or more general transcription factors unwinds 14 base pairs of DNA to form an RNA polymerase-promoter "open complex". In the "open complex" the promoter DNA is unwound and single-stranded; the exposed, single-stranded DNA is referred to as the "transcription bubble."RNA polymerase, assisted by one or more general transcription factors selects a transcription start site in the transcription bubble, binds to an initiating NTP and an extending NTP complementary to the transcription start site sequence, catalyzes bond formation to yield an initial RNA product.
In bacteria, RNA polymerase holoenzyme consists of five subunits: 2 α subunits, 1 β subunit, 1 β' subunit, 1 ω subunit. In bacteria, there is one general RNA transcription factor: sigma. RNA polymerase core enzyme binds to the bacterial general transcription factor sigma to form RNA polymerase holoenzyme and binds to a promoter. In archaea and eukaryotes, RNA polymerase contains subunits homologous to each of the five RNA polymerase subunits in bacteria and contains additional subunits. In archaea and eukaryotes, the functions of the bacterial general transcription factor sigma are performed by multiple general transcription factors that work together. In archaea, there ar
Aquaporins called water channels, are integral membrane proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells facilitating transport of water between cells. The cell membranes of a variety of different bacteria, fungi and plant cells contain aquaporins through which water can flow more into and out of the cell than by diffusing through the phospholipid bilayer. Aquaporin has six membrane-spanning alpha helical domains with both carboxylic and amino terminals on the cytoplasmic side. Two hydrophobic loops contain conserved asparagine-proline-alanine NPA motif; the 2003 Nobel Prize in Chemistry was awarded jointly to Peter Agre for the discovery of aquaporins and Roderick MacKinnon for his work on the structure and mechanism of potassium channels. Genetic defects involving aquaporin genes have been associated with several human diseases including nephrogenic diabetes insipidus and neuromyelitis optica; the mechanism of facilitated water transport and the probable existence of water pores has attracted researchers since 1957.
In most cells, water moves out by osmosis through the lipid component of cell membranes. Due to the high water permeability of some epithelial cells, it was long suspected that some additional mechanism for water transport across membranes must exist. Solomon and his co-workers performed pioneering work on water permeability across the cell membrane in the late 1950s. In the mid-1960s an alternative hypothesis sought to establish that the water molecules partitioned between the water phase and the lipid phase and diffused through the membrane, crossing it until the next interphase where they left the lipid and returned to an aqueous phase. Studies by Parisi, Edelman,Carvounis et al. accented not only the importance of the presence of water channels but the possibility to regulate their permeability properties. In 1990, Verkman's experiments demonstrated functional expression of water channels, indicating that water channels are proteins, it was not until 1992 that the first aquaporin,'aquaporin-1', was reported by Peter Agre, of Johns Hopkins University.
In 1999, together with other research teams, Agre reported the first high-resolution images of the three-dimensional structure of an aquaporin, aquaporin-1. Further studies using supercomputer simulations identified the pathway of water as it moved through the channel and demonstrated how a pore can allow water to pass without the passage of small solutes; the pioneering research and subsequent discovery of water channels by Agre and his colleagues won Agre the Nobel Prize in Chemistry in 2003. Agre said he discovered aquaporins "by serendipity." He had been studying the Rh blood group antigens and had isolated the Rh molecule, but a second molecule, 28 kilodaltons in size kept appearing. At first they thought it was a Rh molecule fragment, or a contaminant, but it turned out to be a new kind of molecule with unknown function, it was present in structures such as kidney tubules and red blood cells, related to proteins of diverse origins, such as in fruit fly brain, the lens of the eye, plant tissue.
However the first report of protein-mediated water transport through membranes was by Gheorghe Benga in 1986, prior to Agre's first publication on the topic. This led to a controversy that Benga's work had been adequately recognized neither by Agre nor by the Nobel Prize Committee. Aquaporins are "the plumbing system for cells". Water moves through cells in an organized way, most in tissues that have aquaporin water channels. For many years, scientists assumed that water leaked through the cell membrane, some water does. However, this did not explain how water could move so through some cells. Aquaporins selectively conduct water molecules in and out of the cell, while preventing the passage of ions and other solutes. Known as water channels, aquaporins are integral membrane pore proteins; some of them, known as aquaglyceroporins transport other small uncharged dissolved molecules including ammonia, CO2, urea. For example, the aquaporin 3 channel has a pore width of 8–10 Ångströms and allows the passage of hydrophilic molecules ranging between 150 and 200 Da.
However, the water pores block ions including protons, essential to conserve the membrane's electrochemical potential difference. Water molecules traverse through the pore of the channel in single file; the presence of water channels increases membrane permeability to water. These are essential for the water transport system in plants and tolerance to drought and salt stresses. Aquaporin proteins are composed of a bundle of six transmembrane α-helices, they are embedded in the cell membrane. The amino and carboxyl ends face the inside of the cell; the amino and carboxyl halves resemble each other repeating a pattern of nucleotides. Some researchers believe that this was created by the doubling of a half-sized gene. Between the helices are five regions that loop into or out of the cell membrane, two of them hydrophobic, with an asparagine–proline–alanine pattern, they create a distinctive hourglass shape, making the water channel narrow in the middle and wider at each end. Another and narrower place in the channel is the "ar/R selectivity filter", a cluster of amino acids enabling the aquaporin to selectively let through or block the passage of different molecules.
Aquaporins form four part clusters in the cell membrane, with each of the four monomers acting as a water channel. Different aquaporins have different sized water channels, the smallest types allowing nothing but water through. X-ray profiles show that aquapor
A morula is an early-stage embryo consisting of 16 cells in a solid ball contained within the zona pellucida. A morula is distinct from a blastocyst in that a morula is a mass of 16 totipotent cells in a spherical shape whereas a blastocyst has a cavity inside the zona pellucida along with an inner cell mass. A morula, if untouched and allowed to remain implanted, will develop into a blastocyst; the morula is produced by a series of cleavage divisions of the early embryo, starting with the single-celled zygote. Once the embryo has divided into 16 cells, it begins to resemble a mulberry, hence the name morula. Within a few days after fertilization, cells on the outer part of the morula become bound together with the formation of desmosomes and gap junctions, becoming nearly indistinguishable; this process is known as compaction.. The cells on the outside and inside become differentially fated into trophoblast and inner cell mass projenitors. A cavity forms inside the morula, by the active transport of sodium ions from trophoblast cells and osmosis of water.
This results in a hollow ball of cells known as the blastocyst. The blastocyst's outer cells will become the first embryonic epithelium; some cells, will remain trapped in the interior and will become the inner cell mass, are pluripotent. In mammals, the ICM will form the "embryo proper", while the trophectoderm will form the placenta and extra-embryonic tissues. However, reptiles have a different ICM; the stages are prolonged and divided in four parts. Cleavage Blastula Marine cephalopod fossil embryos "Regulative development in mammals"
Amino acids are organic compounds containing amine and carboxyl functional groups, along with a side chain specific to each amino acid. The key elements of an amino acid are carbon, hydrogen and nitrogen, although other elements are found in the side chains of certain amino acids. About 500 occurring amino acids are known and can be classified in many ways, they can be classified according to the core structural functional groups' locations as alpha-, beta-, gamma- or delta- amino acids. In the form of proteins, amino acid residues form the second-largest component of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. In biochemistry, amino acids having both the amine and the carboxylic acid groups attached to the first carbon atom have particular importance, they are known as α-amino acids. They include the 22 proteinogenic amino acids, which combine into peptide chains to form the building-blocks of a vast array of proteins.
These are all L-stereoisomers, although a few D-amino acids occur in bacterial envelopes, as a neuromodulator, in some antibiotics. Twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as "standard" amino acids; the other two are selenocysteine, pyrrolysine. Pyrrolysine and selenocysteine are encoded via variant codons. N-formylmethionine is considered as a form of methionine rather than as a separate proteinogenic amino acid. Codon–tRNA combinations not found in nature can be used to "expand" the genetic code and form novel proteins known as alloproteins incorporating non-proteinogenic amino acids. Many important proteinogenic and non-proteinogenic amino acids have biological functions. For example, in the human brain and gamma-amino-butyric acid are the main excitatory and inhibitory neurotransmitters. Hydroxyproline, a major component of the connective tissue collagen, is synthesised from proline. Glycine is a biosynthetic precursor to porphyrins used in red blood cells.
Carnitine is used in lipid transport. Nine proteinogenic amino acids are called "essential" for humans because they cannot be produced from other compounds by the human body and so must be taken in as food. Others may be conditionally essential for medical conditions. Essential amino acids may differ between species; because of their biological significance, amino acids are important in nutrition and are used in nutritional supplements, fertilizers and food technology. Industrial uses include the production of drugs, biodegradable plastics, chiral catalysts; the first few amino acids were discovered in the early 19th century. In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus, subsequently named asparagine, the first amino acid to be discovered. Cystine was discovered in 1810, although its monomer, remained undiscovered until 1884. Glycine and leucine were discovered in 1820; the last of the 20 common amino acids to be discovered was threonine in 1935 by William Cumming Rose, who determined the essential amino acids and established the minimum daily requirements of all amino acids for optimal growth.
The unity of the chemical category was recognized by Wurtz in 1865, but he gave no particular name to it. Usage of the term "amino acid" in the English language is from 1898, while the German term, Aminosäure, was used earlier. Proteins were found to yield amino acids after enzymatic acid hydrolysis. In 1902, Emil Fischer and Franz Hofmeister independently proposed that proteins are formed from many amino acids, whereby bonds are formed between the amino group of one amino acid with the carboxyl group of another, resulting in a linear structure that Fischer termed "peptide". In the structure shown at the top of the page, R represents a side chain specific to each amino acid; the carbon atom next to the carboxyl group is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as alpha amino acids; these include amino acids such as proline which contain secondary amines, which used to be referred to as "imino acids". The alpha amino acids are the most common form found in nature, but only when occurring in the L-isomer.
The alpha carbon is a chiral carbon atom, with the exception of glycine which has two indistinguishable hydrogen atoms on the alpha carbon. Therefore, all alpha amino acids but glycine can exist in either of two enantiomers, called L or D amino acids, which are mirror images of each other. While L-amino acids represent all of the amino acids found in proteins during translation in the ribosome, D-amin
Embryology is the branch of biology that studies the prenatal development of gametes and development of embryos and fetuses. Additionally, embryology encompasses the study of congenital disorders that occur before birth, known as teratology. Embryology has a long history. Aristotle proposed the accepted theory of epigenesis, that organisms develop from seed or egg in a sequence of steps; the alternative theory, that organisms develop from pre-existing miniature versions of themselves, held sway until the 18th century. Modern embryology developed from the work of von Baer, though accurate observations had been made in Italy by anatomists such as Aldrovandi and Leonardo da Vinci in the Renaissance. After cleavage, the dividing cells, or morula, becomes a hollow ball, or blastula, which develops a hole or pore at one end. In bilateral animals, the blastula develops in one of two ways that divide the whole animal kingdom into two halves. If in the blastula the first pore becomes the mouth of the animal, it is a protostome.
The protostomes include most invertebrate animals, such as insects and molluscs, while the deuterostomes include the vertebrates. In due course, the blastula changes into a more differentiated structure called the gastrula; the gastrula with its blastopore soon develops three distinct layers of cells from which all the bodily organs and tissues develop: The innermost layer, or endoderm, give rise to the digestive organs, the gills, lungs or swim bladder if present, kidneys or nephrites. The middle layer, or mesoderm, gives rise to the muscles, skeleton if any, blood system; the outer layer of cells, or ectoderm, gives rise to the nervous system, including the brain, skin or carapace and hair, bristles, or scales. Embryos in many species appear similar to one another in early developmental stages; the reason for this similarity is. These similarities among species are called homologous structures, which are structures that have the same or similar function and mechanism, having evolved from a common ancestor.
Drosophila melanogaster, a fruit fly, is a model organism in biology on which much research into embryology has been done. Before fertilization, the female gamete produces an abundance of mRNA - transcribed from the genes that encode bicoid protein and nanos protein; these mRNA molecules are stored to be used in what will become the developing embryo. The male and female Drosophila gametes exhibit anisogamy; the female gamete is larger than the male gamete because it harbors more cytoplasm and, within the cytoplasm, the female gamete contains an abundance of the mRNA mentioned. At fertilization, the male and female gametes fuse and the nucleus of the male gamete fuses with the nucleus of the female gamete. Note that before the gametes' nuclei fuse, they are known as pronuclei. A series of nuclear divisions will occur without cytokinesis in the zygote to form a multi-nucleated cell known as a syncytium. All the nuclei in the syncytium are identical, just as all the nuclei in every somatic cell of any multicellular organism are identical in terms of the DNA sequence of the genome.
Before the nuclei can differentiate in transcriptional activity, the embryo must be divided into segments. In each segment, a unique set of regulatory proteins will cause specific genes in the nuclei to be transcribed; the resulting combination of proteins will transform clusters of cells into early embryo tissues that will each develop into multiple fetal and adult tissues in development. Outlined below is the process that leads to tissue differentiation. Maternal-effect genes - subject to Maternal inheritance Egg-polarity genes establish the Anteroposterior axis. Zygotic-effect genes - subject to Mendelian inheritance Segmentation genes establish 14 segments of the embryo using the anteroposterior axis as a guide. Gap genes establish 3 broad segments of the embryo. Pair-rule genes define 7 segments of the embryo within the confines of the second broad segment, defined by the gap genes. Segment-polarity genes define another 7 segments by dividing each of the pre-existing 7 segments into anterior and posterior halves.
Homeotic genes use the 14 segments as pinpoints for specific types of cell differentiation and the histological developments that correspond to each cell type. Humans are deuterostomes. In humans, the term embryo refers to the ball of dividing cells from the moment the zygote implants itself in the uterus wall until the end of the eighth week after conception. Beyond the eighth week after conception, the developing human is called a fetus; as as the 18th century, the prevailing notion in western human embryology was preformation: the idea that semen contains an embryo – a preformed, miniature infant, or homunculus – that becomes larger during development. Until the birth of modern embryology through observation of the mammalian ovum by von Baer in 1827, there was no clear scientific understanding of embryology. Only in the late 1950s when ultrasound was first used for uterine scanning, was the true developmental chronology of human fetus available; the competing explanation of embryonic development was epigenesis proposed 2,000 years earlier by