Integration of Nodal and BMP Signals in the Heart Requires FoxH1 to Create Left–Right Differences in Cell Migration Rates That Direct Cardiac Asymmetry

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Failure to properly establish the left–right (L/R) axis is a major cause of congenital heart defects in humans, but how L/R patterning of the embryo leads to asymmetric cardiac morphogenesis is still unclear. We find that asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality by modulating cell migration velocities across the L/R axis. Moreover, we demonstrate that Nodal plays the crucial role in generating asymmetry in the heart and that Bmp signaling via Bmp4 is dispensable in the presence of asymmetric Nodal signaling. In addition, we identify a previously unappreciated role for the Nodal-transcription factor FoxH1 in mediating cell responsiveness to Bmp, further linking the control of these two pathways in the heart. The interplay between these TGFβ pathways is complex, with Nodal signaling potentially acting to limit the response to Bmp pathway activation and the dosage of Bmp signals being critical to limit migration rates. These findings have implications for understanding the complex genetic interactions that lead to congenital heart disease in humans.

Vyšlo v časopise: Integration of Nodal and BMP Signals in the Heart Requires FoxH1 to Create Left–Right Differences in Cell Migration Rates That Direct Cardiac Asymmetry. PLoS Genet 9(1): e32767. doi:10.1371/journal.pgen.1003109
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003109

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Zdroje

1. BurdineRD, SchierAF (2000) Conserved and divergent mechanisms in left-right axis formation. Genes Dev 14 : 763–776.

2. ShenMM (2007) Nodal signaling: developmental roles and regulation. Development 134 : 1023–1034.

3. RamsdellAF (2005) Left-right asymmetry and congenital cardiac defects: getting to the heart of the matter in vertebrate left-right axis determination. Dev Biol 288 : 1–20.

4. ShiraishiI, IchikawaH (2012) Human Heterotaxy Syndrome. Circ J

5. FrancisRJ, ChristopherA, DevineWA, OstrowskiL, LoC (2012) Congenital heart disease and the specification of left-right asymmetry. Am J Physiol Heart Circ Physiol 302: H2102–2111.

6. BisgroveBW, MorelliSH, YostHJ (2003) Genetics of human laterality disorders: insights from vertebrate model systems. Annu Rev Genomics Hum Genet 4 : 1–32.

7. WangJ, GreeneSB, MartinJF (2011) BMP signaling in congenital heart disease: New developments and future directions. Birth Defects Res A Clin Mol Teratol 91 : 441–448.

8. GlickmanNS, YelonD (2002) Cardiac development in zebrafish: coordination of form and function. Semin Cell Dev Biol 13 : 507–513.

9. BakerK, HoltzmanNG, BurdineRD (2008) Direct and indirect roles for Nodal signaling in two axis conversions during asymmetric morphogenesis of the zebrafish heart. Proc Natl Acad Sci U S A 105 : 13924–13929.

10. de Campos-BaptistaMI, HoltzmanNG, YelonD, SchierAF (2008) Nodal signaling promotes the speed and directional movement of cardiomyocytes in zebrafish. Dev Dyn 237 : 3624–3633.

11. RohrS, OttenC, Abdelilah-SeyfriedS (2008) Asymmetric involution of the myocardial field drives heart tube formation in zebrafish. Circ Res 102: e12–19.

12. SmithKA, ChocronS, von der HardtS, de PaterE, SoufanA, et al. (2008) Rotation and asymmetric development of the zebrafish heart requires directed migration of cardiac progenitor cells. Dev Cell 14 : 287–297.

13. ChenJN, van EedenFJ, WarrenKS, ChinA, Nusslein-VolhardC, et al. (1997) Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish. Development 124 : 4373–4382.

14. ChocronS, VerhoevenMC, RentzschF, HammerschmidtM, BakkersJ (2007) Zebrafish Bmp4 regulates left-right asymmetry at two distinct developmental time points. Dev Biol 305 : 577–588.

15. AmackJD, YostHJ (2004) The T box transcription factor no tail in ciliated cells controls zebrafish left-right asymmetry. Curr Biol 14 : 685–690.

16. DaCosta ByfieldS, MajorC, LapingNJ, RobertsAB (2004) SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7. Mol Pharmacol 65 : 744–752.

17. HagosEG, FanX, DouganST (2007) The role of maternal Activin-like signals in zebrafish embryos. Dev Biol 309 : 245–258.

18. YanYT, GritsmanK, DingJ, BurdineRD, CorralesJD, et al. (1999) Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation. Genes Dev 13 : 2527–2537.

19. SchillingTF, ConcordetJP, InghamPW (1999) Regulation of left-right asymmetries in the zebrafish by Shh and BMP4. Dev Biol 210 : 277–287.

20. LenhartKF, LinSY, TitusTA, PostlethwaitJH, BurdineRD (2011) Two additional midline barriers function with midline lefty1 expression to maintain asymmetric Nodal signaling during left-right axis specification in zebrafish. Development 138 : 4405–4410.

21. FurtadoMB, SollowayMJ, JonesVJ, CostaMW, BibenC, et al. (2008) BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4. Genes Dev 22 : 3037–3049.

22. JinSW, BeisD, MitchellT, ChenJN, StainierDY (2005) Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development 132 : 5199–5209.

23. BisgroveBW, EssnerJJ, YostHJ (1999) Regulation of midline development by antagonism of lefty and nodal signaling. Development 126 : 3253–3262.

24. BisgroveBW, EssnerJJ, YostHJ (2000) Multiple pathways in the midline regulate concordant brain, heart and gut left-right asymmetry. Development 127 : 3567–3579.

25. ThisseC, ThisseB (1999) Antivin, a novel and divergent member of the TGFbeta superfamily, negatively regulates mesoderm induction. Development 126 : 229–240.

26. HoltzmanNG, SchoenebeckJJ, TsaiHJ, YelonD (2007) Endocardium is necessary for cardiomyocyte movement during heart tube assembly. Development 134 : 2379–2386.

27. TotongR, SchellT, LescroartF, RyckebuschL, LinYF, et al. (2011) The novel transmembrane protein Tmem2 is essential for coordination of myocardial and endocardial morphogenesis. Development 138 : 4199–4205.

28. SlagleCE, AokiT, BurdineRD (2011) Nodal-Dependent Mesendoderm Specification Requires the Combinatorial Activities of FoxH1 and Eomesodermin. PLoS Genet 7: e1002072 doi:10.1371/journal.pgen.1002072.

29. ChoiJ, DongL, AhnJ, DaoD, HammerschmidtM, et al. (2007) FoxH1 negatively modulates flk1 gene expression and vascular formation in zebrafish. Dev Biol 304 : 735–744.

30. HuangS, MaJ, LiuX, ZhangY, LuoL (2011) Retinoic acid signaling sequentially controls visceral and heart laterality in Zebrafish. J Biol Chem

31. SilvestriC, NarimatsuM, von BothI, LiuY, TanNB, et al. (2008) Genome-wide identification of Smad/Foxh1 targets reveals a role for Foxh1 in retinoic acid regulation and forebrain development. Dev Cell 14 : 411–423.

32. PittlikS, DominguesS, MeyerA, BegemannG (2008) Expression of zebrafish aldh1a3 (raldh3) and absence of aldh1a1 in teleosts. Gene Expr/Patterns 8 : 141–147.

33. HuangCJ, TuCT, HsiaoCD, HsiehFJ, TsaiHJ (2003) Germ-line transmission of a myocardium-specific GFP transgene reveals critical regulatory elements in the cardiac myosin light chain 2 promoter of zebrafish. Dev Dyn 228 : 30–40.

34. LongS, AhmadN, RebagliatiM (2003) The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry. Development 130 : 2303–2316.

35. NaseviciusA, EkkerSC (2000) Effective targeted gene ‘knockdown’ in zebrafish. Nat Genet 26 : 216–220.