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HDAC3 Is Required for Posterior Lateral Line Development in Zebrafish

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Abstract

Histone deacetylases (HDACs) are involved in multiple developmental processes, but their functions in the development of mechanosensory organs are largely unknown. In the present study, we report the presence of HDAC3 in the zebrafish posterior lateral line primordium and newly deposited neuromasts. We used morpholinos to show that HDAC3 knockdown severely disrupts the development of the posterior lateral line and reduces the numbers of neuromasts and sensory hair cells within these organs. In HDAC3 morphants, we also observed decreased cell proliferation and increased apoptosis, which might lead to these defects. Finally, we show that HDAC3 deficiency results in attenuated Fgf signaling in the migrating primordium. In situ hybridizations indicate aberrant expression patterns of Notch signaling pathway genes in HDAC3 morphants. In addition, inhibition of HDAC3 function diminishes cxcr7b and alters cxcl12a expression in the migrating primordium. Our results indicate that HDAC3 plays a crucial role in regulating posterior lateral line (PLL) formation and provide evidence for epigenetic regulation in auditory organ development.

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Acknowledgments

The authors would like to thank Dong Liu and Min Yu for their technical assistance and Yalin Huang for help with the confocal microscope. This work was supported by grants from the Major State Basic Research Development Program of China (973 Program) (2011CB504506, 2015CB965000), the National Natural Science Foundation of China (nos. 81230019, 81470687, 81470692, 81500784), the Program for Changjiang Scholars and Innovative Research Team in Universities (IRT1010), the Jiangsu Province Natural Science Foundation, (BK20140620), the Specialized Research Fund for the Doctor Program of Higher Education (20120071110077), the Fundamental Research Funds for the Central Universities (2242014R30022, NO2013WSN085), the Construction Program of Shanghai Committee of Science and Technology (12DZ2251700), the Major Program of Shanghai Committee of Science and Technology (11441901000), and the China Postdoctoral Science Foundation Funded Project (2014 M551328).

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Authors and Affiliations

  1. Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China

    Yingzi He, Zhengmin Wang, Dongmei Tang, Wenyan Li & Huawei Li

  2. Key Laboratory of Hearing Medicine of National Health and Family Planning Commission, Shanghai, People’s Republic of China

    Zhengmin Wang & Huawei Li

  3. Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People’s Republic of China

    Shaoyang Sun

  4. Co-innovation Center of Neuroregeneration, Key Laboratory for Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu, 210096, People’s Republic of China

    Renjie Chai

  5. State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200031, People’s Republic of China

    Huawei Li

  6. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China

    Huawei Li

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  1. Yingzi He
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  2. Zhengmin Wang
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  3. Shaoyang Sun
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  4. Dongmei Tang
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Correspondence to Zhengmin Wang or Huawei Li.

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Supplement Figure 1

a The HDAC3 protein level in HDAC3-MO-injected embryos is drastically lower than control embryos at 24 hpf. b Gross phenotypic morphology of a control and an HDAC3 morphant embryo. The HDAC3 morphant at 48 hpf shows normal body morphology. Scale bar 200 μm. (DOCX 262 kb)

Supplement Figure 2

RNA in situ hybridization of Wnt/β-catenin (axin2 and lef1) signaling components in the PLL primordia of controls (ConMO; left panels) and HDAC3 morphants (HDAC3-MO; right panels) between 28 and 30 hpf. Expression of axin2 (a and b) and lef1 (c and d) was similar in both controls and HDAC3 morphant embryos. All images show lateral views; anterior is on the left. The primordium is outlined with a dashed line. (DOCX 414 kb)

Supplemental Figure 3

The expression pattern of dkk1 in the PLL primordia. RNA in situ hybridization of dkk1 in the PLL primordia of control (ConMO), bFGF-untreated HDAC3 morphant (HDAC3-MO), bFGF-treated HDAC3 morphant (HDAC3-MO+bFGF) and bFGF-treated control (ConMO+bFGF) between 28 and 30 hpf. HDAC3 knockdown caused a reduction of dkk1 expression, which was rescued by treatment with bFGF. (DOCX 408 kb)

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He, Y., Wang, Z., Sun, S. et al. HDAC3 Is Required for Posterior Lateral Line Development in Zebrafish. Mol Neurobiol 53, 5103–5117 (2016). https://doi.org/10.1007/s12035-015-9433-6

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