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72-707: 1BHT , 1GMN , 1GMO , 1GP9 , 1NK1 , 1SHY , 1SI5 , 2HGF , 2QJ2 , 3HMS , 3HMT , 3HN4 , 3MKP , 3SP8 , 4K3J , 4O3T , 4O3U , 5COE , 5CP9 , 5CS1 , 5CS3 , 5CS5 , 5CS9 , 5CSQ , 5CT1 , 5CT2 , 5CT3 , 4D3C 3082 15234 ENSG00000019991 ENSMUSG00000028864 P14210 Q08048 NM_000601 NM_001010931 NM_001010932 NM_001010933 NM_001010934 NM_010427 NM_001289458 NM_001289459 NM_001289460 NM_001289461 NP_000592 NP_001010931 NP_001010932 NP_001010933 NP_001010934 NP_001276387 NP_001276388 NP_001276389 NP_001276390 NP_034557 Hepatocyte growth factor ( HGF ) or scatter factor ( SF )

144-414: A tyrosine kinase signaling cascade after binding to the proto-oncogenic c-Met receptor. Hepatocyte growth factor is secreted by platelets , and mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. Its ability to stimulate mitogenesis , cell motility, and matrix invasion gives it a central role in angiogenesis , tumorogenesis , and tissue regeneration. It

216-765: A Dishevelled protein that is tethered to the plasma membrane through a Prickle protein and transmembrane Stbm protein. The active Dishevelled activates RhoA GTPase through Dishevelled associated activator of morphogenesis 1 (Daam1) and the Rac protein . Active RhoA is able to induce cytoskeleton changes by activating Roh-associated kinase (ROCK) and affect gene transcription directly. Active Rac can directly induce cytoskeleton changes and affect gene transcription through activation of JNK. The noncanonical Wnt/Ca pathway regulates intracellular calcium levels. Again Wnt binds and activates to Frizzled. In this case however activated Frizzled causes

288-489: A TGF-β superfamily ligand binds to the type II receptor, it recruits a type I receptor and activates it by phosphorylating the serine or threonine residues of its "GS" box. This forms an activation complex that can then phosphorylate SMAD proteins. There are three classes of SMADs: Examples of SMADs in each class: The TGF-β superfamily activates members of the SMAD family, which function as transcription factors. Specifically,

360-427: A bistable organelle at the apical end of each cell. The organelle consists of microtubules and microfilaments in mechanical opposition. It responds to local mechanical perturbations caused by morphogenetic movements. These then trigger traveling embryonic differentiation waves of contraction or expansion over presumptive tissues that determine cell type and is followed by cell differentiation. The cell state splitter

432-408: A complex with c-Met that is able to transduce intracellular signals leading to cell division and cell migration. Paracrine Although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set of receptors and pathways. In fact, different organs in the body - even between different species - are known to utilize

504-462: A consequence of changes in cell adhesive and contractile properties. Following epithelial-mesenchymal transition, cells can migrate away from an epithelium and then associate with other similar cells in a new location. In plants, cellular morphogenesis is tightly linked to the chemical composition and the mechanical properties of the cell wall. During embryonic development, cells are restricted to different layers due to differential affinities. One of

576-443: A coupled G-protein to activate a phospholipase (PLC), which interacts with and splits PIP 2 into DAG and IP 3 . IP 3 can then bind to a receptor on the endoplasmic reticulum to release intracellular calcium stores, to induce calcium-dependent gene expression. The Wnt signaling pathways are critical in cell-cell signaling during normal development and embryogenesis and required for maintenance of adult tissue, therefore it

648-408: A high risk of mortality. Circulating HGF has been also identified as a prognostic marker of severity in patients with hypertension. Circulating HGF has been also suggested as a precocious biomarker for the acute phase of bowel inflammation. Exogenous HGF administered by intravenous injection is cleared rapidly from circulation by the liver , with a half-life of approximately 4 minutes. Dihexa

720-577: A large number of cysteine -rich glycoproteins . The Wnt proteins activate signal transduction cascades via three different pathways, the canonical Wnt pathway , the noncanonical planar cell polarity (PCP) pathway , and the noncanonical Wnt/Ca pathway. Wnt proteins appear to control a wide range of developmental processes and have been seen as necessary for control of spindle orientation, cell polarity, cadherin mediated adhesion, and early development of embryos in many different organisms. Current research has indicated that deregulation of Wnt signaling plays

792-557: A like-to-like manner: E-cadherin (found on many epithelial cells) binds preferentially to other E-cadherin molecules. Mesenchymal cells usually express other cadherin types such as N-cadherin. The extracellular matrix (ECM) is involved in keeping tissues separated, providing structural support or providing a structure for cells to migrate on. Collagen , laminin , and fibronectin are major ECM molecules that are secreted and assembled into sheets, fibers, and gels. Multisubunit transmembrane receptors called integrins are used to bind to

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864-470: A potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction . As well as the well-characterised effects of HGF on epithelial cells , endothelial cells and haemopoietic progenitor cells , HGF also regulates the chemotaxis of T cells into heart tissue. Binding of HGF by c-Met, expressed on T cells, causes the upregulation of c-Met, CXCR3 , and CCR4 which in turn imbues them with

936-651: A response in the receiving cell, that cell must have the appropriate receptors available on the cell membrane to receive the signals, also known as being competent . Additionally, the responding cell must also have the ability to be mechanistically induced. Although the FGF family of paracrine factors has a broad range of functions, major findings support the idea that they primarily stimulate proliferation and differentiation. To fulfill many diverse functions, FGFs can be alternatively spliced or even have different initiation codons to create hundreds of different FGF isoforms . One of

1008-561: A role in tumor formation, because at a cellular level, Wnt proteins often regulated cell proliferation , cell morphology, cell motility , and cell fate. In the canonical pathway , Wnt proteins binds to its transmembrane receptor of the Frizzled family of proteins. The binding of Wnt to a Frizzled protein activates the Dishevelled protein. In its active state the Dishevelled protein inhibits

1080-466: A similar sets of paracrine factors in differential development. The highly conserved receptors and pathways can be organized into four major families based on similar structures: fibroblast growth factor (FGF) family, Hedgehog family, Wnt family, and TGF-β superfamily . Binding of a paracrine factor to its respective receptor initiates signal transduction cascades, eliciting different responses. In order for paracrine factors to successfully induce

1152-408: A technique which has been highly optimized in recent years due to its use in machine learning . This model was limited to the generation of pictures, and is thus bi-dimensional. A similar model to the one described above was subsequently extended to generate three-dimensional structures, and was demonstrated in the video game Minecraft , whose block-based nature made it particularly expedient for

1224-502: A tissue level, ignoring the means of control, morphogenesis arises because of cellular proliferation and motility. Morphogenesis also involves changes in the cellular structure or how cells interact in tissues. These changes can result in tissue elongation, thinning, folding, invasion or separation of one tissue into distinct layers. The latter case is often referred as cell sorting . Cell "sorting out" consists of cells moving so as to sort into clusters that maximize contact between cells of

1296-399: A variety of cancers , including of the lungs , pancreas , thyroid , colon , and breast . Increased expression of HGF has been associated with the enhanced and scarless wound healing capabilities of fibroblast cells isolated from the oral mucosa tissue. Plasma from patients with advanced heart failure presents increased levels of HGF, which correlates with a negative prognosis and

1368-503: Is a paracrine cellular growth, motility and morphogenic factor . It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells , but also acts on haemopoietic progenitor cells and T cells . It has been shown to have a major role in embryonic organ development, specifically in myogenesis , in adult organ regeneration, and in wound healing. Hepatocyte growth factor regulates cell growth, cell motility, and morphogenesis by activating

1440-414: Is an orally active, centrally penetrant small-molecule compound that directly binds to HGF and potentiates its ability to activate its receptor, c-Met. It is a strong inducer of neurogenesis and is being studied for the potential treatment of Alzheimer's disease and Parkinson's disease . Hepatocyte growth factor has been shown to interact with the protein product of the c-Met oncogene, identified as

1512-485: Is essential for the evolution of new forms. Morphogenesis is a mechanical process involving forces that generate mechanical stress, strain, and movement of cells, and can be induced by genetic programs according to the spatial patterning of cells within tissues. Abnormal morphogenesis is called dysmorphogenesis . Some of the earliest ideas and mathematical descriptions on how physical processes and constraints affect biological growth, and hence natural patterns such as

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1584-622: Is expressed in the Sertoli cells involved in spermatogenesis . Indian hedgehog ( IHH ) is expressed in the gut and cartilage, important in postnatal bone growth. Members of the Hedgehog protein family act by binding to a transmembrane " Patched " receptor, which is bound to the " Smoothened " protein, by which the Hedgehog signal can be transduced . In the absence of Hedgehog, the Patched receptor inhibits Smoothened action. Inhibition of Smoothened causes

1656-538: Is focused on the action of the Wnt signaling pathway the regulation of stem cell choice to proliferate and self renew. This action of Wnt signaling in the possible control and maintenance of stem cells, may provide a possible treatment in cancers exhibiting aberrant Wnt signaling. " TGF " (Transforming Growth Factor) is a family of proteins that includes 33 members that encode dimeric , secreted polypeptides that regulate development. Many developmental processes are under its control including gastrulation, axis symmetry of

1728-538: Is important in hematopoiesis (formation of cells in blood). The Kit receptor and related tyrosine kinase receptors actually are inhibitory and effectively suppresses receptor firing. Mutant forms of the Kit receptor, which fire constitutively in a ligand-independent fashion, are found in a diverse array of cancerous malignancies. Research on thyroid cancer has elucidated the theory that paracrine signaling may aid in creating tumor microenvironments. Chemokine transcription

1800-502: Is instrumental in the development of limbs, specifically in its ability to regulate bone growth through paracrine signaling of cytokines. However, mutations in this pathway have been implicated in severe forms of dwarfism: thanatophoric dysplasia (lethal) and achondroplasic dwarfism (viable). This is due to a mutation in a Fgf gene, causing a premature and constitutive activation of the Stat1 transcription factor. Chondrocyte cell division

1872-461: Is not difficult to understand why disruption in Wnt signaling pathways can promote human degenerative disease and cancer . The Wnt signaling pathways are complex, involving many different elements, and therefore have many targets for misregulation. Mutations that cause constitutive activation of the Wnt signaling pathway lead to tumor formation and cancer. Aberrant activation of the Wnt pathway can lead to increase cell proliferation. Current research

1944-615: Is only one co-SMAD, SMAD4 . Non-Smad signaling proteins contribute to the responses of the TGF-β pathway in three ways. First, non-Smad signaling pathways phosphorylate the Smads. Second, Smads directly signal to other pathways by communicating directly with other signaling proteins, such as kinases. Finally, the TGF-β receptors directly phosphorylate non-Smad proteins. This family includes TGF-β1 , TGF-β2 , TGF-β3 , and TGF-β5. They are involved in positively and negatively regulation of cell division ,

2016-503: Is prematurely terminated, resulting in lethal dwarfism. Rib and limb bone growth plate cells are not transcribed. Thus, the inability of the rib cage to expand prevents the newborn's breathing. Research on paracrine signaling through the JAK-STAT pathway revealed its potential in activating invasive behavior of ovarian epithelial cells . This epithelial to mesenchymal transition is highly evident in metastasis . Paracrine signaling through

2088-410: Is secreted as a single inactive polypeptide and is cleaved by serine proteases into a 69-kDa alpha-chain and 34-kDa beta-chain. A disulfide bond between the alpha and beta chains produces the active, heterodimeric molecule. The protein belongs to the plasminogen subfamily of S1 peptidases but has no detectable protease activity. Human HGF plasmid DNA therapy of cardiomyocytes is being examined as

2160-424: Is the so-called French flag model , developed in the sixties. Improvements in computer performance in the twenty-first century enabled the simulation of relatively complex morphogenesis models. In 2020, such a model was proposed where cell growth and differentiation is that of a cellular automaton with parametrized rules. As the rules' parameters are differentiable, they can be trained with gradient descent ,

2232-505: Is upregulated when Ras is in the GTP-bound state. The chemokines are then released from the cell, free to bind to another nearby cell. Paracrine signaling between neighboring cells creates this positive feedback loop. Thus, the constitutive transcription of upregulated proteins form ideal environments for tumors to arise. Effectively, multiple bindings of ligands to the RTK receptors overstimulates

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2304-448: The BMP family are BMP4 and BMP7 . BMP4 promotes bone formation, causes cell death, or signals the formation of epidermis , depending on the tissue it is acting on. BMP7 is crucial for kidney development, sperm synthesis, and neural tube polarization. Both BMP4 and BMP7 regulate mature ligand stability and processing, including degrading ligands in lysosomes. BMPs act by diffusing from

2376-497: The Cubitus interruptus (Ci), Fused, and Cos protein complex attached to microtubules to remain intact. In this conformation, the Ci protein is cleaved so that a portion of the protein is allowed to enter the nucleus and act as a transcriptional repressor . In the presence of Hedgehog, Patched no longer inhibits Smoothened. Then active Smoothened protein is able to inhibit PKA and Slimb, so that

2448-458: The Greek morphê shape and genesis creation, literally "the generation of form") is the biological process that causes a cell , tissue or organism to develop its shape. It is one of three fundamental aspects of developmental biology along with the control of tissue growth and patterning of cellular differentiation . The process controls the organized spatial distribution of cells during

2520-503: The bacteriophage (phage) T4 virion , the morphogenetic proteins encoded by the phage genes interact with each other in a characteristic sequence. Maintaining an appropriate balance in the amounts of each of these proteins produced during viral infection appears to be critical for normal phage T4 morphogenesis. Phage T4 encoded proteins that determine virion structure include major structural components, minor structural components and non-structural proteins that catalyze specific steps in

2592-435: The embryonic development of an organism . Morphogenesis can take place also in a mature organism, such as in the normal maintenance of tissue by stem cells or in regeneration of tissues after damage. Cancer is an example of highly abnormal and pathological tissue morphogenesis. Morphogenesis also describes the development of unicellular life forms that do not have an embryonic stage in their life cycle. Morphogenesis

2664-447: The homodimerized receptor. This conformational change activates the dormant kinase of each RTK on the tyrosine residue. Due to the fact that the receptor spans across the membrane from the extracellular environment, through the lipid bilayer , and into the cytoplasm , the binding of the receptor to the ligand also causes the trans phosphorylation of the cytoplasmic domain of the receptor. An adaptor protein (such as SOS) recognizes

2736-418: The spirals of phyllotaxis , were written by D'Arcy Wentworth Thompson in his 1917 book On Growth and Form and Alan Turing in his The Chemical Basis of Morphogenesis (1952). Where Thompson explained animal body shapes as being created by varying rates of growth in different directions, for instance to create the spiral shell of a snail , Turing correctly predicted a mechanism of morphogenesis,

2808-459: The BMP family were originally found to induce bone formation , as their name suggests. However, BMPs are very multifunctional and can also regulate apoptosis , cell migration , cell division , and differentiation . They also specify the anterior/posterior axis, induce growth, and regulate homeostasis . The BMPs bind to the bone morphogenetic protein receptor type II (BMPR2). Some of the proteins of

2880-450: The Ci protein is not cleaved. This intact Ci protein can enter the nucleus, associate with CPB protein and act as a transcriptional activator , inducing the expression of Hedgehog-response genes. The Hedgehog Signaling pathway is critical in proper tissue patterning and orientation during normal development of most animals. Hedgehog proteins induce cell proliferation in certain cells and differentiations in others. Aberrant activation of

2952-615: The ECM. Integrins bind extracellularly to fibronectin, laminin, or other ECM components, and intracellularly to microfilament -binding proteins α-actinin and talin to link the cytoskeleton with the outside. Integrins also serve as receptors to trigger signal transduction cascades when binding to the ECM. A well-studied example of morphogenesis that involves ECM is mammary gland ductal branching. Tissues can change their shape and separate into distinct layers via cell contractility. Just as in muscle cells, myosin can contract different parts of

Hepatocyte growth factor - Misplaced Pages Continue

3024-507: The HGF receptor ( HGFR ). Both overexpression of the Met/HGFR receptor protein and autocrine activation of Met/HGFR by simultaneous expression of the hepatocyte growth factor ligand have been implicated in oncogenesis. Hepatocyte growth factor interacts with the sulfated glycosaminoglycans heparan sulfate and dermatan sulfate. The interaction with heparan sulfate allows hepatocyte growth factor to form

3096-544: The Hedgehog pathway has been implicated in several types of cancers , Basal Cell Carcinoma in particular. This uncontrolled activation of the Hedgehog proteins can be caused by mutations to the signal pathway, which would be ligand independent, or a mutation that causes overexpression of the Hedgehog protein, which would be ligand dependent. In addition, therapy-induced Hedgehog pathway activation has been shown to be necessary for progression of Prostate Cancer tumors after androgen deprivation therapy . This connection between

3168-425: The Hedgehog signaling pathway and human cancers may provide for the possible of therapeutic intervention as treatment for such cancers. The Hedgehog signaling pathway is also involved in normal regulation of stem-cell populations, and required for normal growth and regeneration of damaged organs. This may provide another possible route for tumorigenesis via the Hedgehog pathway. The Wnt protein family includes

3240-563: The JAK-STAT pathway is necessary in the transition from stationary epithelial cells to mobile mesenchymal cells, which are capable of invading surrounding tissue. Only the JAK-STAT pathway has been found to induce migratory cells. The Hedgehog protein family is involved in induction of cell types and the creation of tissue boundaries and patterning and are found in all bilateral organisms. Hedgehog proteins were first discovered and studied in Drosophila . Hedgehog proteins produce key signals for

3312-752: The Ras-Raf-MAPK pathway, which overexpresses the mitogenic and invasive capacity of cells. In addition to RTK pathway, fibroblast growth factors can also activate the JAK-STAT signaling pathway . Instead of carrying covalently associated tyrosine kinase domains, Jak-STAT receptors form noncovalent complexes with tyrosine kinases of the Jak ( Janus kinase ) class. These receptors bind are for erythropoietin (important for erythropoiesis ), thrombopoietin (important for platelet formation), and interferon (important for mediating immune cell function). After dimerization of

3384-458: The ability to migrate into heart tissue. HGF also promotes angiogenesis in ischemia injury. HGF may further play a role as an indicator for prognosis of chronicity for Chikungunya virus induced arthralgia . High HGF levels correlate with high rates of recovery. Excessive local expression of HGF in the breasts has been implicated in macromastia . HGF is also importantly involved in normal mammary gland development. HGF has been implicated in

3456-429: The activation of transcription factors which enter the nucleus to alter gene expression. Paracrine signaling of growth factors between nearby cells has been shown to exacerbate carcinogenesis . In fact, mutant forms of a single RTK may play a causal role in very different types of cancer. The Kit proto-oncogene encodes a tyrosine kinase receptor whose ligand is a paracrine protein called stem cell factor (SCF), which

3528-461: The activity of the glycogen synthase kinase 3 ( GSK3 ) enzyme. Normally active GSK3 prevents the dissociation of β-catenin to the APC protein, which results in β-catenin degradation. Thus inhibited GSK3, allows β-catenin to dissociate from APC, accumulate, and travel to nucleus. In the nucleus β-catenin associates with Lef/Tcf transcription factor , which is already working on DNA as a repressor, inhibiting

3600-567: The alveoli. Branching morphogenesis is also evident in the ductal formation of the mammary gland . Primitive duct formation begins in development , but the branching formation of the duct system begins later in response to estrogen during puberty and is further refined in line with mammary gland development. Cancer can result from disruption of normal morphogenesis, including both tumor formation and tumor metastasis . Mitochondrial dysfunction can result in increased cancer risk due to disturbed morphogen signaling. During assembly of

3672-632: The body, organ morphogenesis, and tissue homeostasis in adults. All TGF-β ligands bind to either Type I or Type II receptors, to create heterotetramic complexes. The TGF-β pathway regulates many cellular processes in developing embryo and adult organisms, including cell growth , differentiation , apoptosis , and homeostasis . There are five kinds of type II receptors and seven types of type I receptors in humans and other mammals. These receptors are known as "dual-specificity kinases" because their cytoplasmic kinase domain has weak tyrosine kinase activity but strong serine / threonine kinase activity. When

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3744-448: The cells that create them. Growth factor and clotting factors are paracrine signaling agents. The local action of growth factor signaling plays an especially important role in the development of tissues. Also, retinoic acid , the active form of vitamin A , functions in a paracrine fashion to regulate gene expression during embryonic development in higher animals. In insects, Allatostatin controls growth through paracrine action on

3816-401: The corpora allata. In mature organisms, paracrine signaling is involved in responses to allergens , tissue repair, the formation of scar tissue , and blood clotting . Histamine is a paracrine that is released by immune cells in the bronchial tree. Histamine causes the smooth muscle cells of the bronchi to constrict, narrowing the airways. Morphogenesis Morphogenesis (from

3888-559: The cytokine receptors following ligand binding, the JAKs transphosphorylate each other. The resulting phosphotyrosines attract STAT proteins. The STAT proteins dimerize and enter the nucleus to act as transcription factors to alter gene expression. In particular, the STATs transcribe genes that aid in cell proliferation and survival – such as myc. Phenotype and survival of mice after knockout of some JAK or STAT genes: The JAK-STAT signaling pathway

3960-421: The cytoplasm to change its shape or structure. Myosin-driven contractility in embryonic tissue morphogenesis is seen during the separation of germ layers in the model organisms Caenorhabditis elegans , Drosophila and zebrafish . There are often periodic pulses of contraction in embryonic morphogenesis. A model called the cell state splitter involves alternating cell contraction and expansion, initiated by

4032-759: The diffusion of two different chemical signals, one activating and one deactivating growth, to set up patterns of development, decades before the formation of such patterns was observed. The fuller understanding of the mechanisms involved in actual organisms required the discovery of the structure of DNA in 1953, and the development of molecular biology and biochemistry . Several types of molecules are important in morphogenesis. Morphogens are soluble molecules that can diffuse and carry signals that control cell differentiation via concentration gradients. Morphogens typically act through binding to specific protein receptors . An important class of molecules involved in morphogenesis are transcription factor proteins that determine

4104-488: The establishment of limb and body plan of fruit flies as well as homeostasis of adult tissues, involved in late embryogenesis and metamorphosis . At least three "Drosophila" hedgehog homologs have been found in vertebrates: sonic hedgehog, desert hedgehog, and Indian hedgehog. Sonic hedgehog ( SHH ) has various roles in vertebrae development, mediating signaling and regulating the organization of central nervous system, limb, and somite polarity . Desert hedgehog ( DHH )

4176-865: The fate of cells by interacting with DNA . These can be coded for by master regulatory genes , and either activate or deactivate the transcription of other genes; in turn, these secondary gene products can regulate the expression of still other genes in a regulatory cascade of gene regulatory networks . At the end of this cascade are classes of molecules that control cellular behaviors such as cell migration , or, more generally, their properties, such as cell adhesion or cell contractility. For example, during gastrulation , clumps of stem cells switch off their cell-to-cell adhesion, become migratory, and take up new positions within an embryo where they again activate specific cell adhesion proteins and form new tissues and organs. Developmental signaling pathways implicated in morphogenesis include Wnt , Hedgehog , and ephrins . At

4248-493: The formation of the extracellular matrix between cells, apoptosis , and embryogenesis . They bind to TGF-β type II receptor (TGFBRII). TGF-β1 stimulates the synthesis of collagen and fibronectin and inhibits the degradation of the extracellular matrix . Ultimately, it increases the production of extracellular matrix by epithelial cells . TGF-β proteins regulate epithelia by controlling where and when they branch to form kidney, lung, and salivary gland ducts. Members of

4320-443: The idle kinase and activates the RTK pathway. This pathway begins at the cell membrane surface, where a ligand binds to its specific receptor. Ligands that bind to RTKs include fibroblast growth factors , epidermal growth factors, platelet-derived growth factors, and stem cell factor . This dimerizes the transmembrane receptor to another RTK receptor, which causes the autophosphorylation and subsequent conformational change of

4392-448: The morphogenesis sequence. Phage T4 morphogenesis is divided into three independent pathways: the head, the tail and the long tail fibres as detailed by Yap and Rossman. An approach to model morphogenesis in computer science or mathematics can be traced to Alan Turing 's 1952 paper, "The chemical basis of morphogenesis", a model now known as the Turing pattern . Another famous model

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4464-400: The most important functions of the FGF receptors (FGFR) is in limb development. This signaling involves nine different alternatively spliced isoforms of the receptor. Fgf 8 and Fgf 10 are two of the critical players in limb development. In the forelimb initiation and limb growth in mice, axial (lengthwise) cues from the intermediate mesoderm produces Tbx 5, which subsequently signals to

4536-399: The outer ectoderm cells, which will eventually become the lens. Phenotype and survival of mice after knockout of some FGFR genes: Paracrine signaling through fibroblast growth factors and its respective receptors utilizes the receptor tyrosine pathway. This signaling pathway has been highly studied, using Drosophila eyes and human cancers. Binding of FGF to FGFR phosphorylates

4608-518: The phosphorylated tyrosine on the receptor. This protein functions as a bridge which connects the RTK to an intermediate protein (such as GNRP), starting the intracellular signaling cascade. In turn, the intermediate protein stimulates GDP-bound Ras to the activated GTP-bound Ras. GAP eventually returns Ras to its inactive state. Activation of Ras has the potential to initiate three signaling pathways downstream of Ras: Ras→Raf→MAP kinase pathway, PI3 kinase pathway, and Ral pathway. Each pathway leads to

4680-504: The receptors, the phosphorylated receptor complex can activate SMAD2 and SMAD3 through phosphorylation. However, when a BMP ligand binds to the receptors, the phosphorylated receptor complex activates SMAD1 and SMAD5 . Then, the Smad2/3 or the Smad1/5 complexes form a dimer complex with SMAD4 and become transcription factors . Though there are many R-SMADs involved in the pathway, there

4752-431: The same mesoderm to produce Fgf 10. Fgf 10 then signals to the ectoderm to begin production of Fgf 8, which also stimulates the production of Fgf 10. Deletion of Fgf 10 results in limbless mice. Additionally, paracrine signaling of Fgf is essential in the developing eye of chicks. The fgf 8 mRNA becomes localized in what differentiates into the neural retina of the optic cup . These cells are in contact with

4824-412: The same type. The ability of cells to do this has been proposed to arise from differential cell adhesion by Malcolm Steinberg through his differential adhesion hypothesis . Tissue separation can also occur via more dramatic cellular differentiation events during which epithelial cells become mesenchymal (see Epithelial–mesenchymal transition ). Mesenchymal cells typically leave the epithelial tissue as

4896-594: The strongest adhesion move to the center of a mixed aggregates of cells. Moreover, cell-cell adhesion is often modulated by cell contractility, which can exert forces on the cell-cell contacts so that two cell populations with equal levels of the same adhesion molecule can sort out. The molecules responsible for adhesion are called cell adhesion molecules (CAMs). Several types of cell adhesion molecules are known and one major class of these molecules are cadherins . There are dozens of different cadherins that are expressed on different cell types. Cadherins bind to other cadherins in

4968-631: The transcription of the genes it binds. Binding of β-catenin to Lef/Tcf works as a transcription activator, activating the transcription of the Wnt-responsive genes. The noncanonical Wnt pathways provide a signal transduction pathway for Wnt that does not involve β-catenin . In the noncanonical pathways, Wnt affects the actin and microtubular cytoskeleton as well as gene transcription . The noncanonical PCP pathway regulates cell morphology , division , and movement . Once again Wnt proteins binds to and activates Frizzled so that Frizzled activates

5040-590: The type I receptor, activated by the type II receptor, phosphorylates R-SMADs that then bind to the co-SMAD, SMAD4 . The R-SMAD/Co-SMAD forms a complex with importin and enters the nucleus, where they act as transcription factors and either up-regulate or down-regulate in the expression of a target gene. Specific TGF-β ligands will result in the activation of either the SMAD2/3 or the SMAD1/5 R-SMADs . For instance, when activin , Nodal , or TGF-β ligand binds to

5112-428: The ways this can occur is when cells share the same cell-to- cell adhesion molecules . For instance, homotypic cell adhesion can maintain boundaries between groups of cells that have different adhesion molecules. Furthermore, cells can sort based upon differences in adhesion between the cells, so even two populations of cells with different levels of the same adhesion molecule can sort out. In cell culture cells that have

5184-431: Was first proposed to explain neural plate morphogenesis during gastrulation of the axolotl and the model was later generalized to all of morphogenesis. In the development of the lung a bronchus branches into bronchioles forming the respiratory tree . The branching is a result of the tip of each bronchiolar tube bifurcating, and the process of branching morphogenesis forms the bronchi, bronchioles, and ultimately

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