FGF-induced Pea3 Transcription Factors Program the Genetic Landscape for Cell Fate Determination

Overview

Journal PLoS Genet

Specialty Genetics

Date 2018 Sep 7

PMID 30188892

Citations 9

Authors

Ankur Garg

Abdul Hannan

Qian Wang

Tamica Collins

Siying Teng

Mukesh Bansal

Jian Zhong

Keli Xu

Xin Zhang

Affiliations

Soon will be listed here.

Abstract

FGF signaling is a potent inducer of lacrimal gland development in the eye, capable of transforming the corneal epithelium into glandular tissues. Here, we show that genetic ablation of the Pea3 family of transcription factors not only disrupted the ductal elongation and branching of the lacrimal gland, but also biased the lacrimal gland epithelium toward an epidermal cell fate. Analysis of high-throughput gene expression and chromatin immunoprecipitation data revealed that the Pea3 genes directly control both the positive and negative feedback loops of FGF signaling. Importantly, Pea3 genes are also required to suppress aberrant Notch signaling which, if gone unchecked, can compromise lacrimal gland development by preventing the expression of both Sox and Six family genes. These results demonstrate that Pea3 genes are key FGF early response transcriptional factors, programing the genetic landscape for cell fate determination.

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References

Charlot C, Dubois-Pot H, Serchov T, Tourrette Y, Wasylyk B . A review of post-translational modifications and subcellular localization of Ets transcription factors: possible connection with cancer and involvement in the hypoxic response. Methods Mol Biol. 2010; 647:3-30. DOI: 10.1007/978-1-60761-738-9_1. View

Pan Y, Carbe C, Powers A, Zhang E, Esko J, Grobe K . Bud specific N-sulfation of heparan sulfate regulates Shp2-dependent FGF signaling during lacrimal gland induction. Development. 2007; 135(2):301-10. DOI: 10.1242/dev.014829. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Garg A, Zhang X . Lacrimal gland development: From signaling interactions to regenerative medicine. Dev Dyn. 2017; 246(12):970-980. PMC: 5690849. DOI: 10.1002/dvdy.24551. View

Garg A, Bansal M, Gotoh N, Feng G, Zhong J, Wang F . Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis. PLoS Genet. 2017; 13(10):e1007047. PMC: 5656309. DOI: 10.1371/journal.pgen.1007047. View

Entesarian M, Matsson H, Klar J, Bergendal B, Olson L, Arakaki R . Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands. Nat Genet. 2005; 37(2):125-7. DOI: 10.1038/ng1507. View

Govindarajan V, Ito M, Makarenkova H, Lang R, Overbeek P . Endogenous and ectopic gland induction by FGF-10. Dev Biol. 2000; 225(1):188-200. DOI: 10.1006/dbio.2000.9812. View

Carbe C, Hertzler-Schaefer K, Zhang X . The functional role of the Meis/Prep-binding elements in Pax6 locus during pancreas and eye development. Dev Biol. 2012; 363(1):320-9. PMC: 3288747. DOI: 10.1016/j.ydbio.2011.12.038. View

Chi P, Chen Y, Zhang L, Guo X, Wongvipat J, Shamu T . ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours. Nature. 2010; 467(7317):849-53. PMC: 2955195. DOI: 10.1038/nature09409. View

10.

Chen J, Tambalo M, Barembaum M, Ranganathan R, Simoes-Costa M, Bronner M . A systems-level approach reveals new gene regulatory modules in the developing ear. Development. 2017; 144(8):1531-1543. PMC: 5399671. DOI: 10.1242/dev.148494. View

11.

Raible F, Brand M . Tight transcriptional control of the ETS domain factors Erm and Pea3 by Fgf signaling during early zebrafish development. Mech Dev. 2001; 107(1-2):105-17. DOI: 10.1016/s0925-4773(01)00456-7. View

12.

Chen Z, Huang J, Liu Y, Dattilo L, Huh S, Ornitz D . FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands. Development. 2014; 141(13):2691-701. PMC: 4067963. DOI: 10.1242/dev.108944. View

13.

Moloney D, Panin V, Johnston S, Chen J, Shao L, Wilson R . Fringe is a glycosyltransferase that modifies Notch. Nature. 2000; 406(6794):369-75. DOI: 10.1038/35019000. View

14.

Xu J, Wong E, Cheng C, Li J, Sharkar M, Xu C . Eya1 interacts with Six2 and Myc to regulate expansion of the nephron progenitor pool during nephrogenesis. Dev Cell. 2014; 31(4):434-47. PMC: 4282136. DOI: 10.1016/j.devcel.2014.10.015. View

15.

Hicks C, Johnston S, Disibio G, Collazo A, Vogt T, Weinmaster G . Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2. Nat Cell Biol. 2000; 2(8):515-20. DOI: 10.1038/35019553. View

16.

Chotteau-Lelievre A, Desbiens X, Pelczar H, Defossez P, de Launoit Y . Differential expression patterns of the PEA3 group transcription factors through murine embryonic development. Oncogene. 1997; 15(8):937-52. DOI: 10.1038/sj.onc.1201261. View

17.

Zhang Z, Verheyden J, Hassell J, Sun X . FGF-regulated Etv genes are essential for repressing Shh expression in mouse limb buds. Dev Cell. 2009; 16(4):607-13. PMC: 3541528. DOI: 10.1016/j.devcel.2009.02.008. View

18.

Qu X, Carbe C, Tao C, Powers A, Lawrence R, van Kuppevelt T . Lacrimal gland development and Fgf10-Fgfr2b signaling are controlled by 2-O- and 6-O-sulfated heparan sulfate. J Biol Chem. 2011; 286(16):14435-44. PMC: 3077643. DOI: 10.1074/jbc.M111.225003. View

19.

Newbern J, Zhong J, Wickramasinghe R, Li X, Wu Y, Samuels I . Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. Proc Natl Acad Sci U S A. 2008; 105(44):17115-20. PMC: 2579387. DOI: 10.1073/pnas.0805239105. View

20.

Yan J, Enge M, Whitington T, Dave K, Liu J, Sur I . Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites. Cell. 2013; 154(4):801-13. DOI: 10.1016/j.cell.2013.07.034. View