embryology
The Fibroblast Growth Factor
FGF family
START
Index
1. Components
5. Jobs
9.Angiogenesis
2. Importance
10. Migration
6. Proliferation
11. Team
3. Signal
7. Differentiation
4. Type
8. mutations
11. Thanks
12. Thanks
1. FGF Components
Fibroblast growth factor 2 (FGFR2) also known as CD332 (differentiation cluster 332) is a protein that in humans is encoded by the FGFR2 gene located on chromosome 10
The protein encoded
by this gene, is a member of the fibroblast growth factor receptor family, in which amino acid sequences are highly conserved between organs and during development .
يعد البروتين المشفر بواسطة هذا الجين عضوًا في عائلة مستقبلات عامل نمو الخلايا الليفية، حيث يتم حفظ تسلسل الأحماض الأمينية بشكل كبير بين الأعضاء وخلال التطور
Members of the FGFR family
- differ from each other in their ligand affinity and tissue distribution, the representative full-length protein consists of an extracellular region consisting of three immunoglobulin units and one hydrophobic segment extending from the membrane, and a cytoplasmic tyrosine kinase unit the extracellular portion of the protein interacts with factors Overgrowth of fibroblasts initiating a chain of downstream signals which ultimately affects proliferation and differentiation, this family member is a high-affinity receptor for acid growth factor and/or keratinocytes depending on their isomers.
أفراد عائلة (اف جي اف ار) يختلفون عن بعضهم البعض في تقاربهم اللجيني وتوزيع الأنسجة، يتكون البروتين التمثيلي كامل الطول من منطقة خارج الخلية تتألف من ثلاث وحدات من الغلوبولين المناعي وقطاع واحد كاره للماء يمتد من الغشاء، ووحدة كيناز التايروسين السيتوبلازمي، يتفاعل الجزء خارج الخلية من البروتين مع عوامل نمو الخلايا الليفية مما يؤدي إلى بدء سلسلة من الإشارات في اتجاه المصب مما يؤثر في النهاية على التكاثر والتمايز، يعتبر هذا الفرد من أفراد الأسرة مستقبلاً عالي التقارب لعامل نمو الحمض أو الخلية الكيراتينية اعتمادًا على الأشكال الأيسومرية
2. Importance
Fibroblast growth factor (FGF) is a representative growth factor that has shown potential effects on the repair and regeneration of tissues.
عامل نمو الخلايا الليفية (FGF) هو عامل نمو تمثيلي أظهر تأثيرات محتملة على إصلاح وتجديد الأنسجة.
It was originally identified
- as a protein capable of promoting fibroblast proliferation and is now known to comprise 22 members. FGFs exert multiple functions through the binding into and activation of fibroblast growth factor receptors (FGFRs), and the main signaling through the stimulation of FGFRs is the RAS/MAP kinase pathway. FGFs have been utilized for the regeneration of damaged tissues, including skin, blood vessels, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve. Then, the prospective source of FGF for tissue regeneration is used with recombinant human FGF family.
many previous studies administered the FGFs directly to the wound sites, like other growth factors. However, free-FGFs are readily degradable in vivo, leading to loss of biological activity and functions. To gain satisfactory performance, FGFs are adsorbed onto or encapsulated within materials to secure biological activity in a sustained and controllable manner.
3. FGF Signaling
FGFs act as signal molecules that bind and activate FGFRs. Activated FGFRs mediate signaling by recruiting specific molecules that bind to phosphorylated tyrosine at the cytosolic part of the receptor, triggering a number of signaling pathways leading to specific cellular responses.
4. FGFs Type
Approximately two dozen FGF genes have been identified.
The prototypic FGFs, FGF1 and FGF2, were originally isolated from the brain and pituitary as mitogens for cultured fibroblasts. Several FGFs have since been isolated as growth factors for cultured cells. In addition, several FGF genes have been identified by homology-based PCR or searches in DNA databases. A few Fgf genes also have been identified as genes responsible for hereditary diseases or cancer.
The human Fgf gene family comprises 22 members including FGF1-FGF23.FGF15 has not been identified in humans. No other FGF genes have been identified in the complete human genome sequence.
Human FGFs contain ∼150–300 amino acids and have a conserved core of ∼120 amino acids with ∼30–60% identity
The mouse Fgf family also comprises 22 members including FGF1–FGF23 FGF19 has not been identified in the mouse and rat.
FGF15 and FGF19 are likely to be orthologous genes in vertebrates. Except for mouse and rat, the Fgf15/19 orthologues were named Fgf19 in other vertebrates.
5. Working mechanics
Biological Functions of FGFs.FGFs have various biological functions both in vivo and in vitro. lose their biological functional activity.
Biological Functions of FGFs
FGFs exert their physiological roles by binding to high-affinity tyrosine kinase FGFRs on the surface of the target cell.
Therefore, the function of FGFs depends on the FGF signal pathway between the FGF family and FGFRs.
Many studies have reported that FGFs have functions such as cell proliferation, migration, differentiation, and angiogenesis in various cells and tissues.
FGFs have various biological functions
both in vivo and in vitro,
including roles in mitogenesis,
cellular migration, differentiation, angiogenesis, and wound healing.
FGFs exert their physiological roles through binding FGFR and regulating developmental pathways, controlling events such as mesoderm patterning in the early embryo through the development of multiple organ systems.
FGFRs are expressed on many different cell types and regulate key cell behaviors, such as proliferation, differentiation, and survival, which make FGF signaling susceptible to subversion by cancer cells.
Unlike other growth factors, FGFs act in concert with heparin or heparan sulfate proteoglycan (HSPG) to activate FGFRs and induce the pleiotropic responses that lead to a variety of cellular responses induced by this large family of growth factors.
lose their biological functional activity,
primarily due to diffusional loss and/or enzymatic inactivation/degradation.
it is essential to develop appropriate materials and substrates to contain and deliver them to defective regions, which allows their release at a controllable and sustainable rate. A wide range of biomaterials including synthetic and natural polymers and even tissue matrices have been studied as candidate materials to carry FGFs and elicit their therapeutic efficacy in vitro and/or in vivo.
6. Cell Proliferation
Cell proliferation by FGFs has been reported in many cell types, including endothelial cells, stem cells, and epithelial cells.
FGF1 is a proliferative factor for human preadipocytes that may be important to the overall regulation of human adipogenesis. FGF2 induces cell proliferation after flea-specific gene transfer in mice and stimulates the proliferation and survival of neuroepithelial cells isolated from the telencephalon and mesencephalon.
FGF7 is related to epithelial cell growth. FGF10 plays a role in the pathogenesis of prostate cancer via the facilitation of epithelial cell proliferation.
Interestingly, some FGFs stimulate the proliferation of cancer cells as well as normal cells.
7. Cell Differentiation
FGFs also varies with subfamilies
FGF1 and FGF2 play important roles in the initial differentiation of cochlear ganglion neurons in mice.
Moreover, FGF2 stimulates the differentiation of neuroepithelial cells into mature neurons and glia.
FGF7 is essential for the morphogenesis of suprabasal keratinocytes and the establishment of the normal program of keratinocyte differentiation.
Exogenous FGF20 stimulates the differentiation of monkey stem cells into dopaminergic neurons after treatment in vitro.
8. mutations related to disease
Degradation of FGF8 by loss-of-function leads to Kallmann's syndrome (KAL1), a developmental disorder characterized by anosmia and hypogonadism]. FGF10 loss-of-function causes lacrimal-auditory-to-digital (LADD) syndrome, which is characterized by hearing loss, dental anomalies, and lacrimal and salivary gland hypoplasia. Gain-of-function mutations in FGF23 have been identified in hypophosphataemic rickets
Several germline FGF mutations have been identified in human disease, including loss-of-function mutations, and gain-of-function mutations. For instance, loss-of-function in FGF3 is involved with hereditary deafness, leading to total inner ear agenesis in humans.
9. Angiogenesis
Numerous inducers of angiogenesis have been identified, including members of the vascular endothelial growth factor (VEGF) family, angiopoietins, transforming growth factor-alpha and -beta (TGF-alpha and beta), platelet-derived growth factor (PDGF), tumor necrosis factor-alpha (TNF- alpha), interleukins, chemokines, and members of the fibroblast growth factor (FGF) family.
However, only a limited number of the 22 members of the FGF family have been investigated for their angiogenic potential in vitro and in vivo. The angiogenic properties of FGF1 and FGF2 are well known. Specifically, FGF1 and FGF2 induce the promotion of endothelial cell proliferation and the physical organization of endothelial cells into tube-like structures.
Thus,
they promote angiogenesis. FGF1 and FGF2 are more potent angiogenic factors than vascular endothelial growth factor (VEGF) or platelet-derived growth factor (PDGF).
FGF4 also has angiogenic properties.
10. Cell Migration
Cell migration is a central process in the development and maintenance of multicellular organisms.
Tissue formation during embryonic development wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations.
يتطلب تكوين الأنسجة أثناء التئام الجروح والاستجابات المناعية أثناء التطور الجنيني حركة منسقة للخلايا في اتجاهات معينة إلى مواقع محددة.
Apparently, both FGF1 and FGF2 play important roles in the migration of cochlear ganglion neurons in mice.
Cells often migrate in response to and toward specific external signals in a process known as chemotaxis.
Cell migration of FGFs varies with subfamilies.
FGF2 induces cell migration after flea-specific gene transfer in mice and stimulates cell migration of mouse embryonic limb myogenic cells such as FGF4.
FGF7 is known to stimulate migration and plasminogen activity (PA) of normal human keratinocytes.
Similar to FGF2, FGF8 is a potent chemoattractant in the migration of mesencephalic neural crest cells.
THANKS!
Team work
Anwar
Wjood
Rahaf
Dalal
Hajer
FGF FAMILY
HAJER ALMASS
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Transcript
embryology
The Fibroblast Growth Factor FGF family
START
Index
1. Components
5. Jobs
9.Angiogenesis
2. Importance
10. Migration
6. Proliferation
11. Team
3. Signal
7. Differentiation
4. Type
8. mutations
11. Thanks
12. Thanks
1. FGF Components
Fibroblast growth factor 2 (FGFR2) also known as CD332 (differentiation cluster 332) is a protein that in humans is encoded by the FGFR2 gene located on chromosome 10
The protein encoded
by this gene, is a member of the fibroblast growth factor receptor family, in which amino acid sequences are highly conserved between organs and during development .
يعد البروتين المشفر بواسطة هذا الجين عضوًا في عائلة مستقبلات عامل نمو الخلايا الليفية، حيث يتم حفظ تسلسل الأحماض الأمينية بشكل كبير بين الأعضاء وخلال التطور
Members of the FGFR family
أفراد عائلة (اف جي اف ار) يختلفون عن بعضهم البعض في تقاربهم اللجيني وتوزيع الأنسجة، يتكون البروتين التمثيلي كامل الطول من منطقة خارج الخلية تتألف من ثلاث وحدات من الغلوبولين المناعي وقطاع واحد كاره للماء يمتد من الغشاء، ووحدة كيناز التايروسين السيتوبلازمي، يتفاعل الجزء خارج الخلية من البروتين مع عوامل نمو الخلايا الليفية مما يؤدي إلى بدء سلسلة من الإشارات في اتجاه المصب مما يؤثر في النهاية على التكاثر والتمايز، يعتبر هذا الفرد من أفراد الأسرة مستقبلاً عالي التقارب لعامل نمو الحمض أو الخلية الكيراتينية اعتمادًا على الأشكال الأيسومرية
2. Importance
Fibroblast growth factor (FGF) is a representative growth factor that has shown potential effects on the repair and regeneration of tissues.
عامل نمو الخلايا الليفية (FGF) هو عامل نمو تمثيلي أظهر تأثيرات محتملة على إصلاح وتجديد الأنسجة.
It was originally identified
many previous studies administered the FGFs directly to the wound sites, like other growth factors. However, free-FGFs are readily degradable in vivo, leading to loss of biological activity and functions. To gain satisfactory performance, FGFs are adsorbed onto or encapsulated within materials to secure biological activity in a sustained and controllable manner.
3. FGF Signaling
FGFs act as signal molecules that bind and activate FGFRs. Activated FGFRs mediate signaling by recruiting specific molecules that bind to phosphorylated tyrosine at the cytosolic part of the receptor, triggering a number of signaling pathways leading to specific cellular responses.
4. FGFs Type
Approximately two dozen FGF genes have been identified.
The prototypic FGFs, FGF1 and FGF2, were originally isolated from the brain and pituitary as mitogens for cultured fibroblasts. Several FGFs have since been isolated as growth factors for cultured cells. In addition, several FGF genes have been identified by homology-based PCR or searches in DNA databases. A few Fgf genes also have been identified as genes responsible for hereditary diseases or cancer.
The human Fgf gene family comprises 22 members including FGF1-FGF23.FGF15 has not been identified in humans. No other FGF genes have been identified in the complete human genome sequence.
Human FGFs contain ∼150–300 amino acids and have a conserved core of ∼120 amino acids with ∼30–60% identity
The mouse Fgf family also comprises 22 members including FGF1–FGF23 FGF19 has not been identified in the mouse and rat.
FGF15 and FGF19 are likely to be orthologous genes in vertebrates. Except for mouse and rat, the Fgf15/19 orthologues were named Fgf19 in other vertebrates.
5. Working mechanics
Biological Functions of FGFs.FGFs have various biological functions both in vivo and in vitro. lose their biological functional activity.
Biological Functions of FGFs
FGFs exert their physiological roles by binding to high-affinity tyrosine kinase FGFRs on the surface of the target cell.
Therefore, the function of FGFs depends on the FGF signal pathway between the FGF family and FGFRs.
Many studies have reported that FGFs have functions such as cell proliferation, migration, differentiation, and angiogenesis in various cells and tissues.
FGFs have various biological functions
both in vivo and in vitro,
including roles in mitogenesis,
cellular migration, differentiation, angiogenesis, and wound healing.
FGFs exert their physiological roles through binding FGFR and regulating developmental pathways, controlling events such as mesoderm patterning in the early embryo through the development of multiple organ systems.
FGFRs are expressed on many different cell types and regulate key cell behaviors, such as proliferation, differentiation, and survival, which make FGF signaling susceptible to subversion by cancer cells.
Unlike other growth factors, FGFs act in concert with heparin or heparan sulfate proteoglycan (HSPG) to activate FGFRs and induce the pleiotropic responses that lead to a variety of cellular responses induced by this large family of growth factors.
lose their biological functional activity,
primarily due to diffusional loss and/or enzymatic inactivation/degradation.
it is essential to develop appropriate materials and substrates to contain and deliver them to defective regions, which allows their release at a controllable and sustainable rate. A wide range of biomaterials including synthetic and natural polymers and even tissue matrices have been studied as candidate materials to carry FGFs and elicit their therapeutic efficacy in vitro and/or in vivo.
6. Cell Proliferation
Cell proliferation by FGFs has been reported in many cell types, including endothelial cells, stem cells, and epithelial cells.
FGF1 is a proliferative factor for human preadipocytes that may be important to the overall regulation of human adipogenesis. FGF2 induces cell proliferation after flea-specific gene transfer in mice and stimulates the proliferation and survival of neuroepithelial cells isolated from the telencephalon and mesencephalon.
FGF7 is related to epithelial cell growth. FGF10 plays a role in the pathogenesis of prostate cancer via the facilitation of epithelial cell proliferation.
Interestingly, some FGFs stimulate the proliferation of cancer cells as well as normal cells.
7. Cell Differentiation
FGFs also varies with subfamilies
FGF1 and FGF2 play important roles in the initial differentiation of cochlear ganglion neurons in mice.
Moreover, FGF2 stimulates the differentiation of neuroepithelial cells into mature neurons and glia.
FGF7 is essential for the morphogenesis of suprabasal keratinocytes and the establishment of the normal program of keratinocyte differentiation.
Exogenous FGF20 stimulates the differentiation of monkey stem cells into dopaminergic neurons after treatment in vitro.
8. mutations related to disease
Degradation of FGF8 by loss-of-function leads to Kallmann's syndrome (KAL1), a developmental disorder characterized by anosmia and hypogonadism]. FGF10 loss-of-function causes lacrimal-auditory-to-digital (LADD) syndrome, which is characterized by hearing loss, dental anomalies, and lacrimal and salivary gland hypoplasia. Gain-of-function mutations in FGF23 have been identified in hypophosphataemic rickets
Several germline FGF mutations have been identified in human disease, including loss-of-function mutations, and gain-of-function mutations. For instance, loss-of-function in FGF3 is involved with hereditary deafness, leading to total inner ear agenesis in humans.
9. Angiogenesis
Numerous inducers of angiogenesis have been identified, including members of the vascular endothelial growth factor (VEGF) family, angiopoietins, transforming growth factor-alpha and -beta (TGF-alpha and beta), platelet-derived growth factor (PDGF), tumor necrosis factor-alpha (TNF- alpha), interleukins, chemokines, and members of the fibroblast growth factor (FGF) family.
However, only a limited number of the 22 members of the FGF family have been investigated for their angiogenic potential in vitro and in vivo. The angiogenic properties of FGF1 and FGF2 are well known. Specifically, FGF1 and FGF2 induce the promotion of endothelial cell proliferation and the physical organization of endothelial cells into tube-like structures.
Thus,
they promote angiogenesis. FGF1 and FGF2 are more potent angiogenic factors than vascular endothelial growth factor (VEGF) or platelet-derived growth factor (PDGF).
FGF4 also has angiogenic properties.
10. Cell Migration
Cell migration is a central process in the development and maintenance of multicellular organisms.
Tissue formation during embryonic development wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations.
يتطلب تكوين الأنسجة أثناء التئام الجروح والاستجابات المناعية أثناء التطور الجنيني حركة منسقة للخلايا في اتجاهات معينة إلى مواقع محددة.
Apparently, both FGF1 and FGF2 play important roles in the migration of cochlear ganglion neurons in mice.
Cells often migrate in response to and toward specific external signals in a process known as chemotaxis.
Cell migration of FGFs varies with subfamilies.
FGF2 induces cell migration after flea-specific gene transfer in mice and stimulates cell migration of mouse embryonic limb myogenic cells such as FGF4.
FGF7 is known to stimulate migration and plasminogen activity (PA) of normal human keratinocytes.
Similar to FGF2, FGF8 is a potent chemoattractant in the migration of mesencephalic neural crest cells.
THANKS!
Team work
Anwar
Wjood
Rahaf
Dalal
Hajer