Talk:Developmental Signals - Fibroblast Growth Factor

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On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes: References - recent and historic that relates to the topic Additional topic information - currently prepared in draft format Links - to related webpages Topic page - an edit history as used on other Wiki sites Lecture/Practical - student feedback Student Projects - online project discussions. Links: Pubmed Most Recent | Reference Tutorial | Journal Searches Glossary Links Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link Cite this page: Hill, M.A. (2024, May 6) Embryology Developmental Signals - Fibroblast Growth Factor. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Developmental_Signals_-_Fibroblast_Growth_Factor

2012

Prolonged FGF signaling is necessary for lung and liver induction in Xenopus

BMC Dev Biol. 2012 Sep 18;12:27. doi: 10.1186/1471-213X-12-27.

Shifley ET, Kenny AP, Rankin SA, Zorn AM. Source Perinatal Institute, Divisions of Developmental Biology, University of Cincinnati, Cincinnati, OH, 45229, USA. aaron.zorn@cchmc.org. Abstract ABSTRACT: BACKGROUND: FGF signaling plays numerous roles during organogenesis of the embryonic gut tube. Mouse explant studies suggest that different thresholds of FGF signaling from the cardiogenic mesoderm induce lung, liver, and pancreas lineages from the ventral foregut progenitor cells. The mechanisms that regulate FGF dose in vivo are unknown. Here we use Xenopus embryos to examine the hypothesis that a prolonged duration of FGF signaling from the mesoderm is required to induce foregut organs. RESULTS: We show that both mesoderm and FGF signaling are required for liver and lung development in Xenopus; formally demonstrating that this important step in organ induction is conserved with other vertebrate species. Prolonged contact with the mesoderm and persistent FGF signaling through both MEK and PI3K over an extended period of time are required for liver and lung specification. Inhibition of FGF signaling results in reduced liver and lung development, with a modest expansion of the pancreas/duodenum progenitor domain. Hyper-activation of FGF signaling has the opposite effect expanding liver and lung gene expression and repressing pancreatic markers. We show that FGF signaling is cell autonomously required in the endoderm and that a dominant negative FGF receptor decreases the ability of ventral foregut progenitor cells to contribute to the lung and liver buds. CONCLUSIONS: These results suggest that the liver and lungs are specified at progressively later times in development requiring mesoderm contact for different lengths of time. Our data suggest that this is achieved at least in part through prolonged FGF signaling. In addition to providing a foundation for further mechanistic studies on foregut organogenesis using the experimental advantages of the Xenopus system, these data have implications for the directed differentiation of stem cells into foregut lineages.

PMID 22988910

2010

Hormone-like (endocrine) Fgfs: their evolutionary history and roles in development, metabolism, and disease

Cell Tissue Res. 2010 Oct;342(1):1-11. Epub 2010 Aug 24.

Itoh N. Source Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, Japan. itohnobu@pharm.kyoto-u.ac.jp

Abstract

Fibroblast growth factors (Fgfs) are proteins with diverse functions in development, repair, and metabolism. The human Fgf gene family with 22 members can be classified into three groups, canonical, intracellular, and hormone-like Fgf genes. In contrast to canonical and intracellular Fgfs identified in invertebrates and vertebrates, hormone-like Fgfs, Fgf15/19, Fgf21, and Fgf23, are vertebrate-specific. The ancestral gene of hormone-like Fgfs was generated from the ancestral gene of canonical Fgfs by gene duplication early in vertebrate evolution. Later, Fgf15/19, Fgf21, and Fgf23 were generated from the ancestral gene by genome duplication events. Canonical Fgfs act as autocrine/paracrine factors in an Fgf receptor (Fgfr)-dependent manner. In contrast, hormone-like Fgfs act as endocrine factors in an Fgfr-dependent manner. Canonical Fgfs have a heparin-binding site necessary for the stable binding of Fgfrs and local signaling. In contrast, hormone-like Fgfs acquired endocrine functions by reducing their heparin-binding affinity during their evolution. Fgf15/19 and Fgf23 require βKlotho and αKlotho as cofactors, respectively. However, Fgf21 might physiologically require neither. Hormone-like Fgfs play roles in metabolism at postnatal stages, although they also play roles in development at embryonic stages. Fgf15/19 regulates bile acid metabolism in the liver. Fgf21 regulates lipid metabolism in the white adipose tissue. Fgf23 regulates serum phosphate and active vitamin D levels. Fgf23 signaling disorders caused by hereditary diseases or tumors result in metabolic disorders. In addition, serum Fgf19 or Fgf21 levels are significantly increased by metabolic disorders. Hormone-like Fgfs are newly emerging and quite unique in their evolution and function.

PMID: 20730630 http://www.ncbi.nlm.nih.gov/pubmed/20730630

A requirement for FGF signalling in the formation of primitive streak-like intermediates from primitive ectoderm in culture

PLoS One. 2010 Sep 3;5(9):e12555.

Zheng Z, de Iongh RU, Rathjen PD, Rathjen J.

Department of Zoology, University of Melbourne, Parkville, Australia. Abstract BACKGROUND: Embryonic stem (ES) cells hold considerable promise as a source of cells with therapeutic potential, including cells that can be used for drug screening and in cell replacement therapies. Differentiation of ES cells into the somatic lineages is a regulated process; before the promise of these cells can be realised robust and rational methods for directing differentiation into normal, functional and safe cells need to be developed. Previous in vivo studies have implicated fibroblast growth factor (FGF) signalling in lineage specification from pluripotent cells. Although FGF signalling has been suggested as essential for specification of mesoderm and endoderm in vivo and in culture, the exact role of this pathway remains unclear.

METHODOLOGY/PRINCIPAL FINDINGS: Using a culture model based on early primitive ectoderm-like (EPL) cells we have investigated the role of FGF signalling in the specification of mesoderm. We were unable to demonstrate any mesoderm inductive capability associated with FGF1, 4 or 8 signalling, even when the factors were present at high concentrations, nor any enhancement in mesoderm formation induced by exogenous BMP4. Furthermore, there was no evidence of alteration of mesoderm sub-type formed with addition of FGF1, 4 or 8. Inhibition of endogenous FGF signalling, however, prevented mesoderm and favoured neural differentiation, suggesting FGF signalling was required but not sufficient for the differentiation of primitive ectoderm into primitive streak-like intermediates. The maintenance of ES cell/early epiblast pluripotent marker expression was also observed in cultures when FGF signalling was inhibited.

CONCLUSIONS/SIGNIFICANCE: FGF signalling has been shown to be required for the differentiation of primitive ectoderm to neurectoderm. This, coupled with our observations, suggest FGF signalling is required for differentiation of the primitive ectoderm into the germ lineages at gastrulation.

PMID: 20838439