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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Akap12beta supports asymmetric heart development via modulating the Kupffer's vesicle formation in zebrafish

  • Kim, Jeong-gyun (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Kim, Hyun-Ho (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Bae, Sung-Jin (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
  • Received : 2019.04.15
  • Accepted : 2019.06.03
  • Published : 2019.08.31
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Abstract

The vertebrate body plan is accomplished by left-right asymmetric organ development and the heart is a representative asymmetric internal organ which jogs to the left-side. Kupffer's vesicle (KV) is a spherical left-right organizer during zebrafish embryogenesis and is derived from a cluster of dorsal forerunner cells (DFCs). Cadherin1 is required for collective migration of a DFC cluster and failure of DFC collective migration by Cadherin1 decrement causes KV malformation which results in defective heart laterality. Recently, loss of function mutation of A-kinase anchoring protein 12 (AKAP12) is reported as a high-risk gene in congenital heart disease patients. In this study, we demonstrated the role of $akap12{\beta}$ in asymmetric heart development. The $akap12{\beta}$, one of the akap12 isoforms, was expressed in DFCs which give rise to KV and $akap12{\beta}$-deficient zebrafish embryos showed defective heart laterality due to the fragmentation of DFC clusters which resulted in KV malformation. DFC-specific loss of $akap12{\beta}$ also led to defective heart laterality as a consequence of the failure of collective migration by cadherin1 reduction. Exogenous $akap12{\beta}$ mRNA not only restored the defective heart laterality but also increased cadherin1 expression in $akap12{\beta}$ morphant zebrafish embryos. Taken together, these findings provide the first experimental evidence that $akap12{\beta}$ regulates heart laterality via cadherin1.

Keywords

References

  1. Essner JJ, Amack JD, Nyholm MK, Harris EB and Yost HJ (2005) Kupffer's vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut. Development 132, 1247-1260 https://doi.org/10.1242/dev.01663
  2. Matsui T, Thitamadee S, Murata T et al (2011) Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis. Proc Natl Acad Sci U S A 108, 9881-9886 https://doi.org/10.1073/pnas.1017248108
  3. Oteiza P, Koppen M, Concha ML and Heisenberg CP (2008) Origin and shaping of the laterality organ in zebrafish. Development 135, 2807-2813 https://doi.org/10.1242/dev.022228
  4. Desgrange A, Le Garrec JF and Meilhac SM (2018) Left-right asymmetry in heart development and disease: forming the right loop. Development 145, dev162776 https://doi.org/10.1242/dev.162776
  5. van der Linde D, Konings EE, Slager MA et al (2011) Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 58, 2241-2247 https://doi.org/10.1016/j.jacc.2011.08.025
  6. Hartill VL, van de Hoek G, Patel MP et al (2018) DNAAF1 links heart laterality with the AAA+ ATPase RUVBL1 and ciliary intraflagellar transport. Hum Mol Genet 27, 529-545 https://doi.org/10.1093/hmg/ddx422
  7. Gelman IH (2012) Suppression of tumor and metastasis progression through the scaffolding functions of SSeCKS/Gravin/AKAP12. Cancer Metastasis Rev 31, 493-500 https://doi.org/10.1007/s10555-012-9360-1
  8. Choi YK, Kim JH, Kim WJ et al (2007) AKAP12 regulates human blood-retinal barrier formation by downregulation of hypoxia-inducible factor-1alpha. J Neurosci 27, 4472-4481 https://doi.org/10.1523/JNEUROSCI.5368-06.2007
  9. Lee S-W, Kim WJ, Choi YK et al (2003) SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier. Nat Med 9, 900 https://doi.org/10.1038/nm889
  10. Cha JH, Wee HJ, Seo JH et al (2014) AKAP12 mediates barrier functions of fibrotic scars during CNS repair. PLoS One 9, e94695 https://doi.org/10.1371/journal.pone.0094695
  11. Weiser DC, Pyati UJ and Kimelman D (2007) Gravin regulates mesodermal cell behavior changes required for axis elongation during zebrafish gastrulation. Genes Dev 21, 1559-1571 https://doi.org/10.1101/gad.1535007
  12. Kwon HB, Choi YK, Lim JJ et al (2012) AKAP12 regulates vascular integrity in zebrafish. Exp Mol Med 44, 225-235 https://doi.org/10.3858/emm.2012.44.3.017
  13. Kim HH, Kim JG, Jeong J, Han SY and Kim KW (2014) Akap12 is essential for the morphogenesis of muscles involved in zebrafish locomotion. Differentiation 88, 106-116 https://doi.org/10.1016/j.diff.2014.11.002
  14. Streb JW, Kitchen CM, Gelman IH and Miano JM (2004) Multiple promoters direct expression of three AKAP12 isoforms with distinct subcellular and tissue distribution profiles. J Biol Chem 279, 56014-56023 https://doi.org/10.1074/jbc.M408828200
  15. Jin SC, Homsy J, Zaidi S et al (2017) Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat Genet 49, 1593-1601 https://doi.org/10.1038/ng.3970
  16. Kim JG, Bae SJ, Lee HS, Park JH and Kim KW (2017) Claudin5a is required for proper inflation of Kupffer's vesicle lumen and organ laterality. PLoS One 12, e0182047 https://doi.org/10.1371/journal.pone.0182047
  17. Joseph Yost H (1999) Diverse initiation in a conserved left-right pathway? Curr Opin Genet Dev 9, 422-426 https://doi.org/10.1016/S0959-437X(99)80064-1
  18. Tay HG, Schulze SK, Compagnon J et al (2013) Lethal giant larvae 2 regulates development of the ciliated organ Kupffer's vesicle. Development 140, 1550-1559 https://doi.org/10.1242/dev.087130
  19. Gelman IH, Tombler E and Vargas J (2000) A Role for SSeCKS, a major protein kinase C substrate with tumour suppressor activity, in cytoskeletal architecture, formation of migratory processes, and cell migration during embryogenesis. Histochem J 32, 13-26 https://doi.org/10.1023/A:1003950027529
  20. Akakura S, Huang C, Nelson PJ, Foster B and Gelman IH (2008) Loss of the SSeCKS/Gravin/AKAP12 gene results in prostatic hyperplasia. Cancer Res 68, 5096-5103 https://doi.org/10.1158/0008-5472.CAN-07-5619
  21. Sugrue KF, Sarkar AA, Leatherbury L and Zohn IE (2019) The ubiquitin ligase HECTD1 promotes retinoic acid signaling required for development of the aortic arch. Dis Model Mech 12, dmm036491 https://doi.org/10.1242/dmm.036491
  22. Vroomans RMA and Ten Tusscher K (2017) Modelling asymmetric somitogenesis: Deciphering the mechanisms behind species differences. Dev Biol 427, 21-34 https://doi.org/10.1016/j.ydbio.2017.05.010
  23. Robichaux JP, Fuseler JW, Patel SS, Kubalak SW, Hartstone-Rose A and Ramsdell AF (2016) Left-right analysis of mammary gland development in retinoid X receptor-alpha+/- mice. Philos Trans R Soc Lond B Biol Sci 371, 20150416 https://doi.org/10.1098/rstb.2015.0416
  24. Cha JH, Wee HJ, Seo JH et al (2014) Prompt meningeal reconstruction mediated by oxygen-sensitive AKAP12 scaffolding protein after central nervous system injury. Nat Commun 5, 4952 https://doi.org/10.1038/ncomms5952
  25. Cano A, Perez-Moreno MA, Rodrigo I et al (2000) The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2, 76-83 https://doi.org/10.1038/35000025
  26. Gupta K, Pilli VS and Aradhyam GK (2016) Left-right axis asymmetry determining human cryptic gene is transcriptionally repressed by snail. BMC Dev Biol 16, 39 https://doi.org/10.1186/s12861-016-0141-x
  27. Collins MM, Baumholtz AI, Simard A, Gregory M, Cyr DG and Ryan AK (2015) Claudin-10 is required for relay of left-right patterning cues from Hensen's node to the lateral plate mesoderm. Dev Biol 401, 236-248 https://doi.org/10.1016/j.ydbio.2015.02.019
  28. Bae SJ, Shin MW, Kim RH et al (2017) Ninjurin1 assembles into a homomeric protein complex maintained by N-linked glycosylation. J Cell Biochem 118, 2219-2230 https://doi.org/10.1002/jcb.25872
  29. Bae SJ, Shin MW, Son T et al (2019) Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts. Exp Mol Med 51, 7 https://doi.org/10.1038/s12276-018-0201-3