Faculty Opinions recommendation of Cardiac arterial pole alignment is sensitive to FGF8 signaling in the pharynx.

2006 ◽  
Author(s):  
Peter Scambler
Keyword(s):  
Fgf8 Signaling

Cubilin, the Intrinsic Factor-Vitamin B12 Receptor in Development and Disease

2020 ◽  
Vol 27 (19) ◽  
pp. 3123-3150 ◽  
Author(s):  
Renata Kozyraki ◽  
Olivier Cases
Keyword(s):  
Vitamin B12 ◽  
Cancer Progression ◽  
Intrinsic Factor ◽  
Basic Research ◽  
Toxic Substances ◽  
Human Pathology ◽  
Peripheral Membrane Protein ◽  
Epidermal Growth ◽  
Fgf8 Signaling

Gp280/Intrinsic factor-vitamin B12 receptor/Cubilin (CUBN) is a large endocytic receptor serving multiple functions in vitamin B12 homeostasis, renal reabsorption of protein or toxic substances including albumin, vitamin D-binding protein or cadmium. Cubilin is a peripheral membrane protein consisting of 8 Epidermal Growth Factor (EGF)-like repeats and 27 CUB (defined as Complement C1r/C1s, Uegf, BMP1) domains. This structurally unique protein interacts with at least two molecular partners, Amnionless (AMN) and Lrp2/Megalin. AMN is involved in appropriate plasma membrane transport of Cubilin whereas Lrp2 is essential for efficient internalization of Cubilin and its ligands. Observations gleaned from animal models with Cubn deficiency or human diseases demonstrate the importance of this protein. In this review addressed to basic research and medical scientists, we summarize currently available data on Cubilin and its implication in renal and intestinal biology. We also discuss the role of Cubilin as a modulator of Fgf8 signaling during embryonic development and propose that the Cubilin-Fgf8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects. We finally provide experimental elements suggesting that some aspects of Cubilin physiology might be relevant in drug design.

scholarly journals Crkl Deficiency Disrupts Fgf8 Signaling in a Mouse Model of 22q11 Deletion Syndromes

2006 ◽  
Vol 10 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Anne M. Moon ◽  
Deborah L. Guris ◽  
Ji-heui Seo ◽  
Leiming Li ◽  
Jennetta Hammond ◽  
...  
Keyword(s):  
Mouse Model ◽  
22Q11 Deletion ◽  
Fgf8 Signaling ◽  
Deletion Syndromes

Exogenous FGF8 signaling in osteocytes leads to mandibular hypoplasia in mice

Oral Diseases ◽  
2020 ◽  
Vol 26 (3) ◽  
pp. 590-596
Author(s):  
Jue Xu ◽  
Linyan Wang ◽  
Zhen Huang ◽  
YiPing Chen ◽  
Meiying Shao
Keyword(s):  
Mandibular Hypoplasia ◽  
Fgf8 Signaling

Fgf8 is Necessary for Normal Frontonasal Development

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P105-P105
Author(s):  
Maria Wittkopf ◽  
Steven L Goudy
Keyword(s):  
Growth Factor ◽  
Craniofacial Development ◽  
Mutant Mice ◽  
Craniofacial Skeleton ◽  
Craniofacial Malformations ◽  
Complex Process ◽  
Poor Differentiation ◽  
Pas Staining ◽  
Fgf8 Signaling

Problem Craniofacial development is a complex process. We explore the role of ectodermal Fgf8 during craniofacial development in mice. Fgf8 is a multi-functional growth factor known to induce cell migration and differentiation. We hypothesize that Fgf8 is necessary for frontonasal development. To determine its role, we selectively removed Fgf8 signaling in cells expressing the AP2 gene. Methods We generated AP2 Cre Fgf8 f/f R26R mice at e13–18. The embryos are harvested and fixed. They are dehydrated or saturated in 30% sucrose, then embedded in paraffin or OCT compound, respectively, for sectioning. The paraffin sections are used for morphologic examination following H&E and PAS staining. The cryosections are used for X-gal staining and immunofluorescence. Skeletal preparations are used to assess the craniofacial skeleton. Results AP2 Cre mice are examined identifying AP2 expression in the developing epithelium. Gross examination of the AP2 Cre Fgf8 f/f mice reveals severe mid-face shortening and micrognathia. These mice are nonviable due to their severe facial abnormalities. Close inspection reveals prominent eyes that appear normally formed but lack eyelids. The skeletal preparation of the AP2 Cre Fgf8 f/f mouse demonstrates almost absent mandibular development and hypoplastic maxilla. This correlates with the hypoplastic, ill-organized sinus cavities with lack of nasal septum development seen on histologic sections. Examination of the epithelium and oral mucosa of these mutant mice demonstrates a verrucous morphology with poor differentiation. Conclusion Fgf8 expression in the ectoderm appears to be necessary for frontonasal development in mice. Without epithelial Fgf8 expression, the craniofacial and epidermal development is severely affected. Future studies will further characterize the epithelial and mesenchymal phenotype of the AP2 Cre Fgf8 f/f mutant mice. Significance The Fibroblast Growth Factor (Fgf) family is involved in multiple steps of craniofacial formation. Further studies elucidating the specific roles of its members, including Fgf8, will help better understand and manage craniofacial malformations.

scholarly journals FGF8-mediated signaling regulates tooth developmental pace and size during odontogenesis

2020 ◽  
Author(s):  
Chensheng Lin ◽  
Ningsheng Ruan ◽  
Linjun Li ◽  
Yibin Chen ◽  
Xiaoxiao Hu ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Regulatory Mechanism ◽  
Developmental Process ◽  
Growth Control ◽  
Tooth Germ ◽  
Ideal Model ◽  
Dental Tissues ◽  
Ideal Model System ◽  
Fgf8 Signaling ◽  
Human And Mouse

AbstractThe developing human and mouse teeth constitute an ideal model system to study the regulatory mechanism underlying organ growth control due to the fact that their teeth share highly conserved and well-characterized developmental processes and their developmental tempo and size vary notably. In the current study, we manipulated heterogenous recombination between human and mouse dental tissues and demonstrate that the dental mesenchyme dominates the tooth developmental tempo and size and FGF8 could be a critical player during this developmental process. Forced activation of FGF8 signaling in the dental mesenchyme of mice promoted cell proliferation, prevented cell apoptosis via p38 and perhaps PI3K-Akt intracellular signaling, and impelled the transition of the cell cycle from G1-to S-phase in the tooth germ, resulting in the slowdown of the tooth developmental pace and the enlargement of the tooth size. Our results provide compelling evidence that extrinsic signals can profoundly affect tooth developmental tempo and size and the dental mesenchymal FGF8 could be a pivotal factor in controlling developmental pace and size in a non-cell-autonomous manner during mammalian odontogenesis.

Activated Epithelial FGF8 Signaling Induces Fused Supernumerary Incisors

2021 ◽  
pp. 002203452110465
Author(s):  
Y. Chen ◽  
Z. Wang ◽  
C. Lin ◽  
Y. Chen ◽  
X. Hu ◽  
...  
Keyword(s):  
Cell Fate ◽  
De Novo ◽  
Tooth Development ◽  
Epithelial Stem Cells ◽  
Unique Type ◽  
Enamel Epithelium ◽  
Enamel Mineralization ◽  
Dental Epithelium ◽  
Fgf8 Signaling ◽  
The Impact

FGF8, which is specifically expressed in the dental epithelium prior to the E12.5 bud stage, is a key player during odontogenesis, being responsible for the initiation of tooth development. Here, to investigate the impact of persistent FGF8 signaling on tooth development, we forcibly activated FGF8 signaling in the dental epithelium after the bud stage by generating K14-Cre;R26R-Fg8 mice. We found that a unique type of fused supernumerary incisors is formed, although morphologically resembling the features of type II dens invaginatus in humans. Further analysis revealed that ectopically activated epithelial FGF8 alters the cell fate of the incisor lingual outer enamel epithelium, endowing it with odontogenic potential by the activation of several key tooth genes, including Pitx2, Sox2, Lef-1, p38, and Erk1/2, and induces de novo formation of an extra incisor crown lingually in parallel to the original one, leading to the formation of an extra incisor crown and fused with the original incisor eventually. Meanwhile, the overdosed epithelial FGF8 signaling dramatically downregulates the expression of mesenchymal Bmp4, leading to severely impaired enamel mineralization. Based on the location of the extra incisors, we propose that they are likely to be rescued replacement teeth. Our results further demonstrate the essential role of FGF8 signaling for tooth initiation and the establishment of progenitor cells of dental epithelial stem cells during development.

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