Saturday, November 9, 2019
Holiday Decision Making
Name: Luong Thanh Long Class: FB3A CONSUMER BEHAVIOR AND HOLIDAY I- Holiday decision-making is different from the traditional problem-solving model of consumer decision-making: 1) The traditional problem-solving model of consumer decision-making: * Behind the visible act of making a purchase lies a decision process that must be investigated. * The purchase decision process is the stages a buyer passes through in making choices about which products and services to buy. * Five Stages of Consumer Behavior: A. Problem Recognition: Perceiving a Need: Perceiving a difference between a person's ideal and actual situations big enough to trigger a decision. * Can be as simple as noticing an empty milk carton or it can be activated by marketing efforts. B. Information Search: Seeking Value Two steps of information search| Internal search| External search| * Scanning oneââ¬â¢s memory to recall previous experiences with products or brands. * Often sufficient for frequently purchased products. * When past experience or knowledge is insufficient * The risk of making a wrong purchase decision is high * The cost of gathering information is low. * Personal sources, such as friends and family. * Public sources, including various product-rating organizations such as Consumer Reports. * Marketer-dominated sources, such as advertising, company websites, and salespeople| C. Alternative Evaluation: Assessing Value * The information search clarifies the problem for the consumer by: (1) Suggesting criteria to use for the purchase. (2) Yielding brand names that might meet the criteria. (3) Developing consumer value perception. * A consumer's evaluative criteria represent both The objective attributes of a brand (such as locate speed on a portable CD player) * The subjective factors (such as prestige). * These criteria establish a consumer's evoked set * The group of brands that a consumer would consider acceptable from among all the brands in the product class of which he or she is a ware. D. Purchase Decision: Buying Value Three possibilities| From whom to buy| When to buy| Do not buy| which depends on such considerations * Terms of sale * Past experience buying from the seller * Return policy. which can be influenced by * Store atmosphere * Time pressure * a sale * Pleasantness of the shopping experience. | | E. Postpurchase Behavior: Value in Consumption or Use * After buying a product, the consumer compares it with expectations and is either satisfied or dissatisfied. * Satisfaction or dissatisfaction affects * Consumer value perceptions * Consumer communications * Repeat-purchase behavior. * Many firms work to produce positive postpurchase communications among consumers and contribute to relationship building between sellers and buyers. Cognitive Dissonance: The feelings of postpurchase psychological tension or anxiety a consumer often experiences * Firms often use ads or follow-up calls from salespeople in this postpurchase stage to try to convince buyers that they made the right decision. In short, in the traditional problem-solving model of consumer decision-making, people tend to consider and investigate all the needs and desires of a product carefully through a range of steps. There are both internal and external factors affect on the decision-making of consumer. ) Holiday decision-making, as described in the case: * The genetic decision about whether or not to go on holiday was not always the starting point; and sometimes this genetic decision was irrelevant. * ââ¬Å"People have a limited capacity for analysis, and this leads them to break down complex decisions into hierarchical processes and take into consideration a small number of critical variables at each level to make the decision-making process more manageableâ⬠. * ââ¬Å"When confronted by a complex problem, the human brain ââ¬Ësatisfiesââ¬â¢ more than it ââ¬Ëoptimisesââ¬â¢,â⬠explains Nicolau. In this situation, ââ¬Å"the individual will try to choose an option that is sufficiently satisfying, regardless of whether or not it is the best choiceâ⬠. 2 * Final decision and bookings are often made very late. * Informants often expressed post-decision regret, which people strove to reduce. * Searching for holiday information tends to be affected by external factors. II- Compare the information search process, as it is described here, with the search process that consumers might follow for one other product category: Holiday information search process| Consumer search process for one product| * Information collection for a holiday tends to be stopped when the holiday has been booked * Real information are collected during the holiday * Consumer will get more conflicted conscious of information. * People do not prepare their trip in much detail. In contrast, they want to discover unexpected things. * Incidental learning seems to play a bigger role than internal learning. * For only one product, consumer will take more time to collect information of a product and analysis in more details and intensive from lots of sources. * Information collection lasts till they ensure that this information is correct and they can make a comparison with other products. * Consumer tries to avoid unexpected situation. * Information search information tends to be stimulus-based (external)| III- The implications of the findings for managers marketing and promoting holidays: 4P principle plays important role in the man agers marketing. Holidaymaker should make a holiday that meets the needs of customer. If we don't provide a holiday special or offer that helps them with those goals, we are doing them and your business a grave disservice. We also need to survey clients and customers from the current year to see how they can improve in the future. Think about how your channels work together and which channels reach your target customer. Offer a free gift or holiday discount to customers who take the time to complete your survey and do not forget to keep contact with your customer. Customer surplus is a very important area in Marketing mix. Only the marginal consumer is willing to pay just the market price in typical supply and demand equilibrium. The consumers would be willing to pay more than the market price is what makes the demand curve slope downward. The amount that these consumers would be willing to pay, but do not have to pay is known as the consumer surplus. ââ¬âââ¬âââ¬âââ¬âââ¬âââ¬âââ¬âââ¬âââ¬âââ¬âââ¬âââ¬âââ¬âââ¬âââ¬â [ 1 ]. 2 The magazine Tourism Management, Juan Luis Nicolau and Francisco Mas analysed data from 2,491 people gathered by the CIS http://www-rohan. sdsu. edu/~renglish/370/notes/chapt05/
Thursday, November 7, 2019
Oxford Scandal Shakes up the Education World Essays
Oxford Scandal Shakes up the Education World Essays Oxford Scandal Shakes up the Education World Essay Oxford Scandal Shakes up the Education World Essay Oxford is thought to be the pioneer of education all over the world and it comes as an inherent disappointment when a scandal like this comes to the fore. The newest scandal against the ancient university is that of taking students in accordance with their wealth, reports The Guardian. The news, revealed just this week, shocked students and parents across the world because of the inherent knack of meritocracy that Oxford was so well renowned for. This is the reason why many students were rejected to be a part of Oxford last year, since they had to prove that they had a substantial amount of wealth. Not only did that form an elitist society, but also did not give any chances to students from smaller backgrounds who deserved to study at the university. The court proceedings took place this week whereby officials from the Admissions Office had to apologize for their unmentioned criterion. Their claim was that most universities followed the same pattern and it only made sense if Oxford did not miss out. However, coupled with the low acceptance rate and the fee bracket, the judge felt that the argument only made so much sense. However, this practice, it was found, was only limited to postgraduate programs. This raised much hue and cry in the House of Commons where the University Minister, David Willets stayed mum on the issue and simply commented that he knew of the lack of transparency prevalent in the admission process and how that was hindering the talents of several students. The director of graduate admissions, was therefore, made to apologize in court for wrongly depriving students of their right to be able to study in the institution. Jane Elizabeth Sherwoodââ¬â¢s apology was then reiterated back to her as it was found that despite her claims and suggestions, college policy was twisted to suit officials as opposed to students. This not only severely disturbed studentsââ¬â¢ faith in Oxford, but also kept poor students from even applying this year. Officials were disappointed by the precedent that had been broken because of these practices and promised an action to stop this. The college being sued is St. Hughââ¬â¢s. In addition to thirteen thousand pounds asked of students, they were also to pay for their accommodation costs therein, making it impossible for them to afford Oxford. The latest update is that Elizabeth was not incriminated along with several others, because she purported, she had continuously fought for admissions to be made on the ground of meritocracy. It is imperative that education be provided to the best of its extent by college officials and if universities like Oxford have started going on money based agenda, then it is only a matter of time before the rest of UKââ¬â¢s universities decide to flare up their fees and not let poor students attend college courses. It is that kind of attitude that keeps most from achieving what they truly deserve in life.
Tuesday, November 5, 2019
An Introduction to Socioeconomic Status
An Introduction to Socioeconomic Status Socioeconomic status (SES) is a term used by sociologists, economists, and other social scientists to describe the class standing of an individualà or group. It is measured by a number of factors, including income, occupation, and education, and it can have either a positive or negative impact on a persons life.à Who Uses SES? Socioeconomic data is gathered and analyzed by a wide range of organizations and institutions. Federal, state, and local governments all use such data to determine everything from tax rates to political representation. The U.S. Census is one of the best-known means of collecting SES data. Nongovernmental organizations and institutions like the Pew Research Center also collect and analyze such data, as do private companies like Google. But in general, when SES is discussed, its in the context of social science. Primary Factors There are three main factors that social scientists use to calculate socioeconomic status: Income: This is how much a person earns, including wages and salaries, as well as other forms of income such as investments and savings. The definition of income is sometimes expanded to include inherited wealth and intangible assets as well.Education: A persons level of education has a direct impact on their earning ability, with higher earning power leading to more educational opportunities that in turn increase future income potential.Occupation: This factor is more difficult to assess because of its subjective nature. White-collar professions that require a high degree of skilled training, such as physicians or lawyers, tend to require more education and thus return more income than many blue-collar jobs. This data is used to determine the level of ones SES, usually classified as low, middle, and high. But a persons true socioeconomic status doesnt necessarily reflect how a person sees him or herself. Although most Americans would describe themselves as middle class, regardless of their actual income, data from the Pew Research Center shows that only about half of all Americans are truly middle class. Impact The SES of an individual or group can have a profound influence on peoples lives. Researchers have pinpointed several factors that can be affected, including: Physical health: Communities with low socioeconomic status in the U.S. have higher rates of infant mortality, obesity, and cardiovascular health issues.à Mental health: Along with poor physical health, communities with low SES report more cases of depression, suicide, drug abuse, behavioral and developmental issues.General health and welfare: Along with the impact on an individuals well being, socioeconomic status can also have an impact on communities, including rates of crime and poverty. Oftentimes, communities of racial and ethnic minorities in the U.S. feel the effects of low socioeconomic status most directly. People who have physical or mental disabilities, as well as the elderly, are also particularly vulnerable populations. Resources and Further Reading Children, Youth, Families and Socioeconomic Status.à American Psychological Association. Accessed 22 Nov. 2017. Fry, Richard, and Kochhar, Rakesh. Are You in the American Middle Class? Find Out with Our Income Calculator. PewResearch.org. 11 May 2016. Tepper, Fabien. What is Your Social Class? Take Our Quiz to Find Out! The Christian Science Monitor. 17 Oct. 2013.
Sunday, November 3, 2019
Video summary Essay Example | Topics and Well Written Essays - 250 words - 4
Video summary - Essay Example E.g. if they would breed with the normal salmon. However, the company that is involved has argued that these fish are sterile. The FDA is yet to decide if the genetically modified fish will carry a special label. Farmers in Arkansas are facing huge losses because their crops have been infested with a type of weed known as the ââ¬Ëpigweedââ¬â¢. The weed is native to North America. Farmers have over the years been able to fight the weed using special chemicals. However, the chemicals have suddenly stopped working. The weed has adapted to the herbicides that were being used to kill them. The weed grows 3 inches a day and kills crops and destroys farm machinery like combine harvesters and cotton pickers. The farmers have now resulted to the traditional way of dealing with weed (using manual labor) which is slow and expensive. Scientists believe that the weed is now resistant to the herbicides used to kill it and a new herbicide needs to be developed. This might take close to seven
Thursday, October 31, 2019
MKTG 406 = MID EXAM & FINAL EXAM Assignment Example | Topics and Well Written Essays - 6250 words
MKTG 406 = MID EXAM & FINAL EXAM - Assignment Example This can be anything, a stable income or job, etc. The next level of needs which is requirement by the person is the need of love and society. The sense of belongingness is his concern at this stage. He or she starts a family and wants to become a part of the society. The next step in the level of needs is the requirement of self esteem. The person wishes to have a successful carrier and wants to be known for his success. He or she thinks himself or herself to be special. Once the self esteem stage has been achieved, the person goes on to the final level of needs known as the self-actualization. This need is way more important than anything; the aspirations come into play over here. Now having discussed the Maslowââ¬â¢s Hierarchy, let us go on to relating these 5 levels of needs with marketing. As the person goes through the different level of needs, he is always influenced by the some products or services at some point of time. In the first step where the person is looking for the basic needs such as food and shelter, he or she will try to select a food is cheap at the same time nutritious, the advertisement displayed or shown will play a major role in his choice. Similarly, in the second stage the person is looking for security and safety. The security can job or life insurance. Again in this situation, the various firms will try to divert his or her mind to purchase their product or services by saying how different and exclusive their services are. This way the person may or may not get manipulated in purchasing the above services. Again in the next three stages also there are various forms of marketing involved which are used against the consumers. For e xample Vodafone might call a person saying that he or she is their most valued customer and that is he or she is being offered a new mobile connection free of charge. This in return tends to affect the person emotionally and the person will most likely go ahead with the deal. Another
Tuesday, October 29, 2019
The Export-Led Growth Model Essay Example | Topics and Well Written Essays - 1750 words
The Export-Led Growth Model - Essay Example Chinaââ¬â¢s model is rooted in the double transition of demographic and structural transformation. China economy has tremendously managed the double-digit growth rates from the period when it began economic transformation. This enabled the country to move from a planned to a mixed economy where the market plays the significant roles in resource allocation. Thus, despite the political, social and economic problems associated with the rapid growth in China economies, export-led growth has tremendously enabled China to increase their profitability levels, balance their finances, exceed their debts and trigger their export growth rate.Export-led growth model have been successful in many economies that employ this model for creating economic transformation. The export-led model is significant because it has enabled many economies to increase their profitability levels, balance their finances and exceed their debts. China has benefited from the export-led model since they started using it because this model has enabled them to increase their profitability levels. China was ranked the second largest economies that have emerged and improved in terms of economic performance in the global market. This model has not only enabled them to increase their profitability level but also to balance their finances; thus enabling China to emerge as the successful economies in Asian markets.It has also triggered export growth rate in the China market; thus creating higher export levels.... This model has not only enabled them to increase their profitability level but also to balance their finances; thus enabling China to emerge as the successful economies in Asian markets. It has also triggered export growth rate in the China market; thus creating higher export levels in a rising spiral cycle. For instance, the GDP (Gross Domestic Products) in China market expanded by 2%, in the year 2012 and indicated in figure 1 below. Historically, the GDP average rate was 2.06% from 2011 and the record indicated the 1.50 % low in 2012 as indicated in figure1 below. China is one of the second economies after the United States that has improved their export rate in the global market. China has varied industries that export multiple products to diverse countries across the globe. The rise of population growth rate has enabled them to improve their economic performance because of rich markets because of both rich markets both in the domestic and the international markets. For instance, the National Bureau of Statistics of China reveals that the GDP for the China economy was 51,932.2 billion in the year 2012; thus contributing to economic expansion of 7.9 percent. Figure 1: GDP Growth Rate in China markets The implementation model of export-led growth has significantly contributed to increased rapid growth in the China markets. For the last three decades, China economy has grown to the average rates, which exceed 9%; thus, it is widely admired by other nations (Razmi 2008, p. 1). Furthermore, the growth has been accompanied by the reduction levels in poverty; thus enabling the China market to be ranked among the leading and emerging economies in the Asian nations. However, the trajectory of rapid growth in China has created political, social made
Sunday, October 27, 2019
Fibroblast Growth Factors (FGFs) in Neural Induction
Fibroblast Growth Factors (FGFs) in Neural Induction Abstract Neural induction represents the first stage in the formation of the vertebrate nervous system from embryonic ectoderm. Fibroblast Growth Factors (FGFs), initially identified for their mitogenic and angiogenic roles in bovine brain extracts, are now known to have many developmental roles in particular that of neural induction, comprising of a family of 22 FGFs. Spemann and Mangold (1924) pioneered the study of neural induction through the identification of the organizer. Early work in amphibians suggested that neural fate was instructed by signals from Spemanns organiser or dorsal mesoderm. Over a decade ago, the default model proposed that neural induction was the direct consequence from inhibition of bone morphogenetic proteins (BMPs) found in Xenopus laevis, not taking into consideration neural induction in avian embryos. Consequently many experimental studies, in the chick, subsequent to this finding conflicted the idea that BMP inhibition was the only necessary step required suggesting that FGFs were required at an earlier stage prior to BMP inhibition. Much controversy has surrounded the role of FGFs in neural induction but now it is widely accepted to have a role in both amphibians and amniotes. Fibroblast Growth Factors in neural induction Structure and Function: FGFs broken down Fibroblast Growth Factors (FGFs) regulate a vast array of developmental processes, including, limb development, neural induction and neural development (Bà ¶ttcher and Niehrs, 2005). FGFs play an important role in development of an organism by regulating cellular differentiation, proliferation and migration and are involved in tissue-injury repair (Itoh and Ornitz, 2004). The early FGFs, FGF1 and FGF2 (also known as acidic and basic FGF, respectively) were first discovered from bovine brain and pituitary extracts and identified for their mitogenic and angiogenic activities (Gospodarowicz et al., 1974). Additionally, a number of family members were found revealing a total of 22 FGFs in humans ranging from 17 to 34 kDa in molecular mass in vertebrates. The nomenclature extends to FGF23 but in humans FGF19 is the equivalent to mouse Fgf15 (Ornitz and Itoh, 2001). Also the FGFs have been organised into seven subfamilies based on sequence comparisons. FGFs show conservation through species, especially across the vertebrate species in gene structure and amino-acid sequence. FGF sequences are yet to be found in unicellular organisms such as yeast (Saccharomyces cerevisiae) and bacteria (Escherichia Coli) (Itoh and Ornitz, 2004). Interestingly, an Fgf-like gene has been encoded in the nuclear polyhedrosis virus genome (Ayres et al., 1994). In protostomes, there are far fewer FGFs in contrast to vertebrates, as two (let-756 and egl-17) have been found in Caenorhabditis elegans and three (branchless, pyramus and thisbe) in Drosophila (Mason, 2007). Most FGFs have amino-terminal signal peptides (Fig. 1 (a)) and are secreted from cells. FGFs 9, 16 and 20 lack this signal peptide but nevertheless are still secreted (Ornitz and Itoh, 2001). FGF1 and FGF2 lack these signal sequences and are secreted by non-canonical pathways, however they can be found on the cell surface and within the extracellular matrix. Golfarb (2005) suggests that FGFs 11-14 do not interact with FGF receptors (FGFRs) and are not secreted but instead localise to the cell nucleus. Fig. 1 (above) illustrates the structural features of the FGF polypeptide (a). A signal sequence (shaded grey) can be seen here within the amino terminus and is present in most FGFs. All FGFs contain a core region (Fig. 1 (a)) containing around 120 amino acids of which 6 are identical amino acids residues and 28 are highly conserved (Goldfarb, 1996). The black boxes (numbered 1 to 12) represent the location of à ² strands within the core. The three dimensional structure of FGF2 (b) can also be seen where the heparin binding region (yellow) includes residues between à ²1 and à ²2 strands and in à ²10 and à ²11 strands. FGFs have a high affinity for heparan sulfate proteoglycans (HSPG) and require heparan sulphate to activate one of four transmembrane receptor tyrosine kinases (FGFR1-4) in all vertebrates. FGFR5 has been identified recently, however most action is mediated via FGFR1-4 (Powers et al., 2000). FGFRs are membrane associated class IV receptor tyrosine kinases (RTKs). The FGFR tyrosine kinase receptors (Fig. 2 B) include 3 immunoglobulin (Ig) domains and a heparin binding sequence which requires heparan sulphate to be activated (McKeehan et al., 1998). HSPG are low affinity receptors that are unable to transmit a biological signal but act as co-factors for activation and regulation of an interaction between FGFs and FGFRs. Fig. 2 (above) illustrates a two dimensional generic FGF (A) and a FGFR (B) protein. The structure of a FGF (A) coincides with that of Fig. 1, containing a signal sequence in the amino-terminus and the conserved core region containing HSPG and receptor-binding sites. The main features of FGFRs (B) include 3-Immunoglobulin domains, an acidic box (AB) which lies between IgI and IgII, heparin-binding domain, Cell Adhesion Molecule (CAM)-homology domain, transmembrane domain and a split tyrosine kinase enzyme domain for catalytic activity and binding of adaptor proteins. The Ig domains in the extracellular region of a FGFR are required for FGF binding and regulate binding affinity and ligand specificity. Multiple alternative splicing that generates a range of FGFR1-4 receptor isoforms with transformed ligand binding properties provides diversity (Olsen et al., 2006). For example, FGF2 interacts with all four receptors FGFR1-4 whereas FGF7 only interacts with the FGFR2 IIIb isoform (a splice variant of FGF2; expressed in epithelial cells). Ligand-receptor binding specificity is affected by alternative splicing particularly in the C-terminal region of the third immunoglobulin loop in FGFR1-3 which produces IIIb or IIIc isoforms (Mason, 2007). Table 1 (below) illustrates the specificity of the FGF ligands for particular FGFR isoforms. This table is useful yet evidence from in vitro may appear misleading as in vivo involves influence from co-factors such as HSPG (Mohammadi et al., 2005). Table 1 (above) shows there are seven FGFR isoforms (FGFR1b; FGFR1c; FGFR2b; FGFR2c; FGFR3b; FGFR3c and FGFR4) that FGF1 through to FGF23 variously bind. Alternative mRNA splicing of FGFR1-3, particularly in the carboxy-terminal half of the third extracellular immunoglobulin loop (Ig-domain III), derives the b and c isoforms. HSPGs are necessary co-factors in activation of FGFRs by FGFs and evidence has found the ternary complex to comprise of FGF-FGFR-HSPG in a 2:2:1 ratio (Mohammadi et al., 2005). The co-binding of HSPG prevents proteolysis and thermal denaturation (Itoh and Ornitz, 2004). HSPG binding of FGF induces dimerization of FGFR, followed by transphosphorylation of receptor subunits, initiating an intracellular signalling cascade. FGF signalling: Its a cellular game Following formation of the FGF-HSPG-FGFR complex several downstream signalling pathways are activated (Fig. 3 below). This includes three pathways, the Ras/Mitogen-activated protein kinase (MAPK) pathway, Phosphoinositide 3-kinase (PI3K)/ Akt pathway and phospholipase C- (PLC )/ Ca2+/ protein kinase C (PKC) pathway. These pathways are mediated via docking proteins (such as FGF receptor substrate (FRS) and Grb2 in the Ras/MAPK pathway) that recruit downstream enzymes. The Ras/MAPK pathway (Fig. 3) is initiated via Grb2 (a docking protein) where its SH2 domain binds to the tyrosine phosphorylated FRS2 in response to activation of the FGFR receptor (Kouhara et al., 1997). Grb2 binds to SOS (son of sevenless; a guanine nucleotide exchange factor) via a SH3 domain on the Grb2 molecule. This Grb2-SOS complex activates SOS which promotes the dissociation of GDP from Ras so it is able to bind GTP for its activation. Activated Ras activates RAF (MAPKKK) which is normally held in a closed conf ormation by the 14-3-3 protein. Once activated, RAF phosphorylates and activates mitogen-activated and extracellular signal-regulated kinase (MEK (MAPKK)) which in turn phosphorylates ERK1/2 (MAPK). MAPK then translocates into the nucleus to phosphorylate specific transcription factors of the Ets family which in turn activate expression of FGF target genes. In addition, it is also evident from Fig. 3 that active ERK itself can antagonise FRS activity. Activation of the PI3K/Akt pathway (Fig. 3) is by binding of Gab1 (Grb2-associated-binding protein 1) to FRS2 indirectly via Grb2. In the presence of Gab1, activation of PI3K stimulates the Akt pathway which suggests FGFs have anti-apoptotic effects in the developing nervous system (Mason, 2007). In addition, PI3K can bind to a phosphorylated tyrosine residue of FGFR directly. The third way in which the PI3K/Akt pathway is activated is by activated Ras inducing membrane localisation of the PI3K catalytic subunit. PLC- /Ca2+/PKC pathway is also activated when a tyrosine residue is autophosphorylated in the carboxy terminal of the FGFR. PLC- hydrolyses phosphatidylinositol to produce inositol trisphosphate (IP3) and diacylglycerol (DAG) which stimulates calcium release and activates PKC, respectively. PKC has also been found to activate the Ras/MAPK pathway independent of Ras but dependent on c-Raf (Ueda et al., 1996). Fig. 3 also indicated that the final activated components, of the three signalling pathways mentioned, translocate into the nucleus to activate specific transcription factors of the Ets family (particularly Ets1, Pea3, and Erm) which activate expression of FGF target genes and in turn these feedback (Fig, 4) to regulate intracellular signalling (Dailey et al., 2005). Most of the proteins produced function as feedback inhibitors (as seen in Fig. 4), including Sprouty (Spry), Sef and MAP Kinase phosphatase 3 (MKP3) which modulate particularly the Ras/Erk pathway at different levels (Mason, 2007). In contrast, stimulation of the fibronectin leucine-rich transmembrane type III (XFLRT3) protein causes FGF signalling to be positively regulated (Bà ¶ttcher et al., 2003). Sprouty (Spry) was one of the first identified feedback regulators of the FGF pathway. Thisse and Thisse (2005) found Spry to antagonise FGF Signalling by gain and/or loss of function experiments in mouse. Spry acts at the level of Raf and/or Grb2 (Fig. 4). Gain and/or loss of function experiments in zebrafish demonstrated that Sef antagonises FGF signalling (Fig. 4) acting at level of MEK and ERK (Tsang et al., 2002). Mouse studies have suggested that FGFR signalling is required for Dusp6 transcription which codes for MKP3 (Ekerot et al., 2008). From this study it was also found that MKP3 acts as a negative regulator of ERK activity (as seen in Fig. 4). Sef and XFLRT3 are located at the membrane (Fig. 4) and carry out antagonising actions with FGFR directly. FGF signalling can be regulated at different levels, from the membrane all the way down to the level of phosphorylation of MAPK and it is important also to know that FGFs have been detected in the nucleus (Mason, 2007). Most of the downstream target genes as described earlier are feedback inhibitors (Spry, Sef and MKP3) but FGF signals are also known to interact with many other important pathways such as transforming growth factor-à ² (TGF-à ²), Hedgehog (HH), Notch and Wnt (Gerhart, 1999). Therefore, in conjunction with these, FGFs are responsible for development of most organs of the vertebrate body. In the nervous system, FGFs have been implicated to play a role in early developmental processes, such as neural induction, patterning and proliferation (Umemori, 2009). Neural induction: The Default Model Spemann and Mangold (1924) pioneered the study of neural induction, which is defined as the process by which naive ectodermal cells aquire a neural fate. Their work involved demonstrating that tissue from the dorsal lip of the frog Xenopus laevis blastopore could induce a second ectopic nervous system (Fig. 5 above left) when implanted onto the ventral side of a host gastrula embryo. The second ectopic nervous system was host derived indicating that the graft was important in determining cell fate. This region, located on the dorsal side of an amphibian embryo, was named the Spemann organizer as it could direct the neighbouring ectodermal cells to form nervous system instead of epidermis. Although the organizer (group of dorsal mesodermal cells) was found to be present in many species (Hamburger, 1988) it was the Xenopus laevis which gave an insight into the molecular events involved in neural induction in vertebrates (Hemmati-Brivanlou et al., 1994). This was particularly because amphibians were found to be ideal experimental models for the study of neural induction as neurulation initiated within twelve hours after fertilisation (Weinstein and Hemmati-Brivanlou, 1997). It was implied that signals from the organizer provide instructions to the ectoderm to form neural tissue therefore for many decades the view was that the default state of the ectoderm was to produce epidermis. The first challenges to this model came from studies making use of dissociated cell cultures (Sato and Sargent, 1989). It was found that when animal caps were cultured intact that epidermis formed but neural tissue arose from animal caps that had been dissociated for prolonged periods (as seen in Fig. 6 below). This led to the idea that intact tissue may block the formation of neural tissue by presence of neural inhibitors which are diluted out when the tissue is dissociated. Recent research has found that the default nature of the ectoderm is to produce neural tissue that requires inhibition of a neural inhibitor from the ectoderm. Before considering the process of neural induction I would like to take a step back and describe the three germ layers of the embryo. Following fertilisation, the zygote undergoes stages of cleavage to eventually form a gastrula with three germ layers (in triploblastic animals) usually only visible in vertebrate animals. The Germ layers will eventually give rise to all of the animals organs through a process known as organogenesis. The three layers include, the ectoderm (outermost), endoderm (innermost) and mesoderm (which is between the ectoderm and endoderm) layers. The Endoderm gives rise to the lung, thyroid and pancreas. The mesoderm forms the skeleton, skeletal muscle, the urogenital system, heart and blood. The outermost layer, the ectoderm which is of concern here, gives rise to the epidermis and nervous system. It is at gastrulation that the vertebrate ectoderm is competent to differentiate into neural tissue or epidermis. Unless told otherwise, the default nature of the ect oderm is to produce neural tissue and this was outlined as the default model. The Default model of vertebrate neural induction, discovered over a decade ago in Xenopus, proposed that in the presence of bone morphogenetic protein (BMP), a signalling molecule of the TGF-à ² superfamily, causes the ectoderm to give rise to an epidermal cell fate (Stern, 2006; Muà ±oz-Sanjuan and Brivanlou, 2002). In support of this model, consistent with the idea that BMP activity inhibits neural fates, animal caps which had been injected with RNA encoding effectors of BMP4 (Smad 1/5 or Msx1) neuralization did not occur. Conversely, it was found that inhibition of BMP activity in the ectoderm is essential for a neural fate which forms the basis of the default model of neural induction. Inhibition of BMP is achieved through direct binding of BMP antagonists emitted from the organizer (Wilson and Hemmati-Brivanlou, 1997). These BMP antagonists include chordin (Sasai et al., 1995), noggin (Lamb et al., 1993) and follistatin (Hemmati-Brivanlou et al., 1994) which bind to BMPs extra cellularly to prevent its interaction with its own receptor (Hemmati-Brivanlou and Melton, 1997). These molecules have direct neural activity which means they induce formation of neural tissue in the ectoderm without forming mesoderm. It was initially believed that these molecules acted as ligands to bring about neural tissue formation. Experiments found that there was conservation through species, identifying that chordin was homologous to the short gastrulation (sog) gene found in Drosophila which has been shown to antagonize the BMP homologue decapentaplegic (dpp) (Wharton et al., 1993), suggesting that these molecules might act as inhibitors rather than inducers and that these inhibitory mechanisms have been conserved from arthropods through to vertebrates. It was experiments (Fig. 6) showing that dissociated ectodermal explants would become neural tissue in absence of inducing signals from the organizer (Sato and Sargent, 1989). Evidence found that neural induction resulted from inhibition of the TGF-à ² pathway as expression of dominant-negative activin receptor gave rise to neural fates in amphibian ectoderms (Hemmati-Brivanlou and Melton, 1994). It was found that chordin, noggin, follistatin and molecules such as Cerberus and Xnr3 (Xenopus nodal related 3) bound to BMP in the extracellular space inhibiting its action (Hemmati-Brivanlou and Melton, 1997) leading to the much debated default model of neural induction. Neural Induction: FGFs get it started Support for the default model still remains, mainly in Xenopus, but other work (especially in chick and mouse) suggests a more complex mechanism (Streit et al., 1998). It has been established that the BMP pathway is involved in determining ectodermal cell fate (Wilson and Hemmati-Brivanlou, 1997) but it still remains to be proved conclusive if BMP inhibition is required for neural induction alone or if other pathways act separately or with BMP inhibition. In the chick embryo it has been found that naive epiblast cells do not respond to BMP antagonists until previous exposure to organizer signals for five hours (Streit et al., 1998). Striet et al. (2000) grafted an organizer to observe the genes induced in the epiblast within this time period. A gene ERNI (early response to neural induction) was identified as a coiled coil domain with a tyrosine phosphorylation site and found to be expressed throughout the region that later contributes to the nervous system at pre-primitive streak stages (Hatada and Stern, 1994). Striet et al. (2000) findings made ERNI the earliest known marker after a response to organizer signals, prior to even Sox3 (induced by the node in 3 hours (Streit and Stern, 1999)). FGFs are becoming more evident that they have a major role in neural induction as it has been shown to begin before gastrulation, before BMP antagonists even appear (Wilson et al., 2000). In the chick, it has been found that FGFs have the role of blocking BMP signalling and promoting neural differentiation (Wilson et al., 2000). In ascidians, FGF signalling is the main mechanism of neural induction with BMP antagonism playing a role in later development (Lemaire et al., 2002). In frogs and fish, in contrast, FGFs do not have a certain role in neural induction and is believed their primary role is BMP inhibition (Pera et al., 2003). Exposure of the chick epiblast to an implanted organiser for around 5 hours induces Sox3 (an early neural plate marker) (Stern, 2005). After removal of the implanted organiser, chordin can be used to stabilise it (Striet et al., 1998) which implies that before the ectoderm can respond to BMP antagonists it must be exposed to 5 hours of signals from the organizer. During these 5 hours, several genes become activated such as, ERNI (early response to neural induction) which becomes active after 1 hour (Streit et al., 2000) and Churchill (Chch) after about 4 hours (Sheng et al., 2003). These are both induced by FGF and not BMP inhibition, indicating the importance of FGFs in early neural induction. Churchill which is expressed in the neural plate inhibits brachyury, a transcription factor, which as a result suppresses mesoderm formation by preventing cell ingression. In the chick, FGF8 is expressed in the hypoblast, prior to gastrulation before Hensens node appears (the chick equivalent to the organizer) indicating that neural induction is in fact able to begin before gastrulation. This is important because ERNI and Sox3 mark neural induction and require FGF signalling (Stern, 2005). Streit et al. (2000) found that FGF8 coated beads induce ERNI as efficiently as the node within 1-2 h without inducing brachury and also the expression of Sox3. These results indicate FGFs to be possible early signals in neural induction. It is FGF8 which has been identified as the best candidate because it is expressed in the anterior part of the str
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