A deficiency in SUMOylation activity disrupts multiple pathways leading to neural tube and heart defects in Xenopus embryos

BMC Genomics

Kyle M. Dubiak¹  Michelle M. Bertke²  Paul W. Huber³  Laura Cronin⁴  Erliang Zeng⁵ 

[1] 0000 0001 2168 0066, grid.131063.6, Department of Chemistry and Biochemistry, University of Notre Dame, 46556, Notre Dame, Indiana, USA;0000 0001 2168 0066, grid.131063.6, Department of Chemistry and Biochemistry, University of Notre Dame, 46556, Notre Dame, Indiana, USA;0000 0001 0941 7177, grid.164295.d, Present Address: College of Computer, Mathematical, and Natural Sciences, University of Maryland, 20742, College Park, MD, USA;0000 0001 2168 0066, grid.131063.6, Department of Chemistry and Biochemistry, University of Notre Dame, 46556, Notre Dame, Indiana, USA;0000 0001 2168 0066, grid.131063.6, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, Indiana, USA;0000 0001 2168 0066, grid.131063.6, Center for Stem Cells and Regenerative Medicine, University of Notre Dame, 46556, Notre Dame, Indiana, USA;Department of Computer Science and Engineering, Chennai, India;Department of Computer Science and Engineering, Chennai, India;0000 0004 1936 8294, grid.214572.7, Present Address: Division of Biostatistics and Computational Biology, Iowa Institute for Oral Health Research, University of Iowa, 52242, Iowa City, IA, USA;0000 0004 1936 8294, grid.214572.7, Present Address: Department of Preventive & Community Dentistry, College of Dentistry, University of Iowa, 52242, Iowa City, IA, USA;0000 0004 1936 8294, grid.214572.7, Present Address: Department of Biostatistics, University of Iowa, 52242, Iowa City, IA, USA;0000 0004 1936 8294, grid.214572.7, Present Address: Department of Biomedical Engineering, University of Iowa, 52242, Iowa City, IA, USA;

关键词: SUMO;    Heart development;    Neural tube development;    Congenital birth defects;    Non-canonical Wnt signaling;    Planar cell polarity;   

DOI  :  10.1186/s12864-019-5773-3

来源: publisher

【 摘 要 】

BackgroundAdenovirus protein, Gam1, triggers the proteolytic destruction of the E1 SUMO-activating enzyme. Microinjection of an empirically determined amount of Gam1 mRNA into one-cell Xenopus embryos can reduce SUMOylation activity to undetectable, but nonlethal, levels, enabling an examination of the role of this post-translational modification during early vertebrate development.ResultsWe find that SUMOylation-deficient embryos consistently exhibit defects in neural tube and heart development. We have measured differences in gene expression between control and embryos injected with Gam1 mRNA at three developmental stages: early gastrula (immediately following the initiation of zygotic transcription), late gastrula (completion of the formation of the three primary germ layers), and early neurula (appearance of the neural plate). Although changes in gene expression are widespread and can be linked to many biological processes, three pathways, non-canonical Wnt/PCP, snail/twist, and Ets-1, are especially sensitive to the loss of SUMOylation activity and can largely account for the predominant phenotypes of Gam1 embryos. SUMOylation appears to generate different pools of a given transcription factor having different specificities with this post-translational modification involved in the regulation of more complex, as opposed to housekeeping, processes.ConclusionsWe have identified changes in gene expression that underlie the neural tube and heart phenotypes resulting from depressed SUMOylation activity. Notably, these developmental defects correspond to the two most frequently occurring congenital birth defects in humans, strongly suggesting that perturbation of SUMOylation, either globally or of a specific protein, may frequently be the origin of these pathologies.

【 授权许可】

CC BY