Evidence-Based Theory for Integrated Genome Regulation of Ontogeny--An Unprecedented Role of Nuclear FGFR1 Signaling

Overview

Journal J Cell Physiol

Specialties Cell Biology
Physiology

Date 2016 Jan 6

PMID 26729628

Citations 18

Authors

Michal K Stachowiak

Ewa K Stachowiak

Affiliations

Soon will be listed here.

Abstract

Genetic experiments have positioned the fgfr1 gene at the top of the gene hierarchy that governs gastrulation, as well as the subsequent development of the major body axes, nervous system, muscles, and bones, by affecting downstream genes that control the cell cycle, pluripotency, and differentiation, as well as microRNAs. Studies show that this regulation is executed by a single protein, the nuclear isoform of FGFR1 (nFGFR1), which integrates signals from development-initiating factors, such as retinoic acid (RA), and operates at the interface of genomic and epigenomic information. nFGFR1 cooperates with a multitude of transcriptional factors (TFs), and targets thousands of genes encoding for mRNAs, as well as miRNAs in top ontogenic networks. nFGFR1 binds to the promoters of ancient proto-oncogenes and tumor suppressor genes, in addition to binding to metazoan morphogens that delineate body axes, and construct the nervous system, as well as mesodermal and endodermal tissues. The discovery of pan-ontogenic gene programming by integrative nuclear FGFR1 signaling (INFS) impacts our understanding of ontogeny, as well as developmental pathologies, and holds new promise for reconstructive medicine, and cancer therapy.

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References

Peng H, Myers J, Fang X, Stachowiak E, Maher P, Martins G . Integrative nuclear FGFR1 signaling (INFS) pathway mediates activation of the tyrosine hydroxylase gene by angiotensin II, depolarization and protein kinase C. J Neurochem. 2002; 81(3):506-24. DOI: 10.1046/j.1471-4159.2002.00833.x. View

Myers J, Martins G, Ostrowski J, Stachowiak M . Nuclear trafficking of FGFR1: a role for the transmembrane domain. J Cell Biochem. 2003; 88(6):1273-91. DOI: 10.1002/jcb.10476. View

Buervenich S, Carmine A, Arvidsson M, Xiang F, Zhang Z, Sydow O . NURR1 mutations in cases of schizophrenia and manic-depressive disorder. Am J Med Genet. 2000; 96(6):808-13. DOI: 10.1002/1096-8628(20001204)96:6<808::aid-ajmg23>3.0.co;2-e. View

Young T, Deschamps J . Hox, Cdx, and anteroposterior patterning in the mouse embryo. Curr Top Dev Biol. 2009; 88:235-55. DOI: 10.1016/S0070-2153(09)88008-3. View

Stachowiak E, Roy I, Lee Y, Capacchietti M, Aletta J, Prasad P . Targeting novel integrative nuclear FGFR1 signaling by nanoparticle-mediated gene transfer stimulates neurogenesis in the adult brain. Integr Biol (Camb). 2009; 1(5-6):394-403. DOI: 10.1039/b902617g. View

Pownall M, Isaacs H, Slack J . Two phases of Hox gene regulation during early Xenopus development. Curr Biol. 1998; 8(11):673-6. DOI: 10.1016/s0960-9822(98)70257-x. View

Stachowiak M, Birkaya B, Aletta J, Narla S, Benson C, Decker B . "Nuclear FGF receptor-1 and CREB binding protein: an integrative signaling module". J Cell Physiol. 2014; 230(5):989-1002. DOI: 10.1002/jcp.24879. View

Dunham-Ems S, Pudavar H, Myers J, Maher P, Prasad P, Stachowiak M . Factors controlling fibroblast growth factor receptor-1's cytoplasmic trafficking and its regulation as revealed by FRAP analysis. Mol Biol Cell. 2006; 17(5):2223-35. PMC: 1446089. DOI: 10.1091/mbc.e05-08-0749. View

Maira M, Martens C, Philips A, Drouin J . Heterodimerization between members of the Nur subfamily of orphan nuclear receptors as a novel mechanism for gene activation. Mol Cell Biol. 1999; 19(11):7549-57. PMC: 84765. DOI: 10.1128/MCB.19.11.7549. View

10.

Mallo M, Alonso C . The regulation of Hox gene expression during animal development. Development. 2013; 140(19):3951-63. DOI: 10.1242/dev.068346. View

11.

White R, Schilling T . How degrading: Cyp26s in hindbrain development. Dev Dyn. 2008; 237(10):2775-90. PMC: 2880953. DOI: 10.1002/dvdy.21695. View

12.

Kam R, Deng Y, Chen Y, Zhao H . Retinoic acid synthesis and functions in early embryonic development. Cell Biosci. 2012; 2(1):11. PMC: 3325842. DOI: 10.1186/2045-3701-2-11. View

13.

Halaban R, Kwon B, Ghosh S, Delli Bovi P, Baird A . bFGF as an autocrine growth factor for human melanomas. Oncogene Res. 1988; 3(2):177-86. View

14.

Gao C, Chen Y . Dishevelled: The hub of Wnt signaling. Cell Signal. 2009; 22(5):717-27. DOI: 10.1016/j.cellsig.2009.11.021. View

15.

Stachowiak M, Moffett J, Maher P, Tucholski J, Stachowiak E . Growth factor regulation of cell growth and proliferation in the nervous system. A new intracrine nuclear mechanism. Mol Neurobiol. 1998; 15(3):257-83. DOI: 10.1007/BF02740663. View

16.

Duboule D . The rise and fall of Hox gene clusters. Development. 2007; 134(14):2549-60. DOI: 10.1242/dev.001065. View

17.

Stachowiak E, Fang X, Myers J, Dunham S, Stachowiak M . cAMP-induced differentiation of human neuronal progenitor cells is mediated by nuclear fibroblast growth factor receptor-1 (FGFR1). J Neurochem. 2003; 84(6):1296-312. DOI: 10.1046/j.1471-4159.2003.01624.x. View

18.

Wahl M, Deng C, Lewandoski M, Pourquie O . FGF signaling acts upstream of the NOTCH and WNT signaling pathways to control segmentation clock oscillations in mouse somitogenesis. Development. 2007; 134(22):4033-41. DOI: 10.1242/dev.009167. View

19.

Stachowiak M, Fang X, Myers J, Dunham S, Berezney R, Maher P . Integrative nuclear FGFR1 signaling (INFS) as a part of a universal "feed-forward-and-gate" signaling module that controls cell growth and differentiation. J Cell Biochem. 2003; 90(4):662-91. DOI: 10.1002/jcb.10606. View

20.

Maira M, Martens C, Batsche E, Gauthier Y, Drouin J . Dimer-specific potentiation of NGFI-B (Nur77) transcriptional activity by the protein kinase A pathway and AF-1-dependent coactivator recruitment. Mol Cell Biol. 2003; 23(3):763-76. PMC: 140697. DOI: 10.1128/MCB.23.3.763-776.2003. View