Knockdown of zebrafish YY1a can downregulate the phosphatidylserine (PS) receptor expression, leading to induce the abnormal brain and heart development.

Wei-Lun Shiu,Kuan-Rong Huang,Jen-Leih Wu,Jo-Chi Hung,Jiann-Ruey Hong

doi:10.1186/s12929-016-0248-1

Wei-Lun Shiu, Kuan-Rong Huang + Show 3 more

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https://doi.org/10.1186/s12929-016-0248-1

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Abstract

BackgroundYin Yang 1 (YY1) is a ubiquitously expressed GLI-Kruppel zinc finger-containing transcriptional regulator. YY1 plays a fundamental role in normal biologic processes such as embryogenesis, differentiation, and cellular proliferation. YY1 effects on the genes involved in these processes are mediated via initiation, activation, or repression of transcription depending upon the context in which it binds. The role of the multifunctional transcription factor Yin Yang 1 (YY1) in tissue development is poorly understood. In the present, we investigated YY1a role in developing zebrafish on PSR-mediated apoptotic cell engulfment during organic morphogenesis.ResultsYY1a is first expressed 0.5 h post-fertilization (hpf), in the whole embryo 12 hpf, and in brain, eyes, and heart 72 hpf by in situ hybridization assay. The nucleotide sequence of zebrafish YY1a transcription factor (clone zfYY1a; HQ 166834) was found to be similar to that of zebrafish YY1a (99 % sequence identity; NM 212617). With the loss-of-function assay, YY1a knockdown by a morpholino oligonucleotide led to downregulation of the phosphatidylserine engulfing receptor zfPSR during embryonic segmentation and to the accumulation of a large number of dead apoptotic cells throughout the entire early embryo, especially in the posterior area. Up to 24 hpf, these cells interfered with embryonic cell migration and cell-cell interactions that normally occur in the brain, heart, eye, and notochord. Finally, with gain-of-function assay, defective morphants could be rescued by injecting both YY1a mRNA and PSR mRNA and trigger resumption of normal development.ConclusionsTaken together, our results suggest that YY1a regulates PS receptor expression that linked to function of PSR-phagocyte mediated apoptotic cell engulfment during development, especially the development of organs such as the brain and heart. YY1a/PSR-mediated engulfing system may involve in diseases.

Highlights

Yin Yang 1 (YY1) is a ubiquitously expressed GLI-Kruppel zinc finger-containing transcriptional regulator
We named zebrafish YY1a (zfYY1) (HQ 166834) gene is equal to YY1a (NM 212617) gene
We found that YY1-morpholino oligonucleotides (MO) (25 ng) injection apparently reduced phosphatidylserine receptor (PSR) expression throughout the embryo (Fig. 5b, c, as indicated by arrows; cf. with Fig. 5b, a [wild type] and Fig. 5B, b [control MO injection]) at 12 hpf and reduced PSR expression in brain and somites (Fig. 5b, f, as indicated by arrows; cf. with Fig. 5b, d [wild type] and Fig. 5b, e [control MO injection]) at 24 hpf

Summary

Introduction

Yin Yang 1 (YY1) is a ubiquitously expressed GLI-Kruppel zinc finger-containing transcriptional regulator. YY1 effects on the genes involved in these processes are mediated via initiation, activation, or repression of transcription depending upon the context in which it binds. Shiu et al Journal of Biomedical Science (2016) 23:31 genes, most of which have yet to be validated as YY1 target genes in vivo These studies suggest important roles for YY1 in the control of cell growth, apoptosis, and oncogenic transformation. Mice heterozygous for the YY1 gene (yy1+/−) display a mild developmental delay and a subset of these animals exhibit neurulation defects and exencephaly [21] While these observations strongly suggest that YY1 acts during late embryogenesis, early embryonic lethality caused by constitutive loss of function has precluded investigation of the YY1 requirement at later developmental stages [22]. Whether the YY1a involve in early embryonic development is still uncover

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