Mga Modulates Bmpr1a Activity by Antagonizing Bs69 in Zebrafish

Sun, Xiaoyun; Chen, Ji; Zhang, Yanyong; Munisha, Mumingjiang; Dougan, Scott T.; Sun, Yuhua

doi:10.3389/fcell.2018.00126

Cited by 9 publications

(15 citation statements)

References 39 publications

(70 reference statements)

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“…Co-immunoprecipitations were performed with the Dynabeads Protein G (Life Technologies, 10004D) according to the manufacturer’s instructions 33 . Briefly, 1.5 mg Dynabeads was conjugated with antibodies or IgG overnight at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

“…Protein-protein interaction assay using a rabbit reticulocyte lysate system has been described previously 33 . Tagged-ADNP, Tagged-ADNP mutants, Tagged-β-Catenin and Tagged-β-Catenin mutants were synthesized using the TNT coupled reticulocyte lysate system according to the manual (Promega, L5020, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The whole-mount immunofluorescence experiments were performed as described 33 . Briefly, 48 hpf zebrafish embryos were fixed in 4% paraformaldehyde overnight at 4 °C and then underwent proteinase K treatment for 8 minutes at RT.…”

Section: Methodsmentioning

confidence: 99%

“…WISH was performed as described previously 33 . For making the RNA probes, total RNA was extracted from zebrafish embryos, and cDNAs were made by RT-PCR.…”

Section: Methodsmentioning

confidence: 99%

“…d Representative morphology of 1 dpf adnpa-/- adnpb-/- embryos. The ventralized phenotypes (V1-V3) were according to the DV patterning index 33 . e Representative morphology of 1 dpf adnpa overexpressing embryos.…”

Section: Supplementary Figmentioning

confidence: 99%

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ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

Sun

Peng

Cao

et al. 2019

Preprint

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5 ADNP (Activity Dependent Neuroprotective Protein) is proposed as a neuroprotective 6 protein whose aberrant expression has been frequently linked to neural developmental 7 disorders, including the Helsmoortel-Van der Aa syndrome. However, its role in 8 neural development and pathology remains unclear. Using mESC (mouse embryonic 9 stem cell) directional neural differentiation as a model, we show that ADNP is 10 required for ESC neural induction and neuronal differentiation by maintaining Wnt 11 signaling. Mechanistically, ADNP functions to maintain the proper protein levels of 12 β-Catenin through binding to its armadillo domain which prevents its association with 13 key components of the degradation complex: Axin and APC. Loss of ADNP promotes 14 the formation of the degradation complex and hyperphosphorylation of β-Catenin by 15 GSK3β and subsequent degradation via ubiquitin-proteasome pathway, resulting in 16 down-regulation of key neuroectoderm developmental genes. We further show that 17 ADNP plays key role in cerebellar neuron formation. Finally, adnp gene disruption in 18 zebrafish embryos recapitulates key features of the mouse phenotype, including the 19 reduced Wnt signaling, defective embryonic cerebral neuron formation and the 20 massive neuron death. Thus, our work provides important insights into the role of 21 ADNP in neural development and the pathology of the Helsmoortel-Van der Aa 22 syndrome caused by ADNP gene mutation. 23 24 42 of mouse embryos. 43 De novo mutations in ADNP gene have recently been linked to neural 44 developmental disorders, including the Helsmoortel-Van der Aa syndrome 6 . Patients 45 display multiple symptoms, usually manifesting in early childhood with features such 46 as intellectual disability, facial dysmorphism, motor dysfunction and developmental 47 65 development which would be useful for understanding the pathology of the 66 Helsmoortel-Van der Aa syndrome caused by ADNP mutation. 67 . 68 69 70 Results 71Generation and characterization of Adnp-/-ESCs. To understand the molecular 72 function of ADNP, we generated Adnp mutant ESCs by using CRISPR/Cas9 73 technology. gRNAs were designed to target the 3' end of exon 4 of mouse Adnp gene 74 ( Fig. 1a). We have successfully generated 2 Adnp mutant alleles (-4 and -5 bp), 75 revealed by DNA genotyping around the CRISPR targeting site ( Fig. 1b). ADNP 76 protein was hardly detectable in Adnp-/-ESCs by Western blot using ADNP 77 antibodies from different resources ( Fig. 1c), which strongly indicated that the mutant 78 alleles are functional nulls. 79 In the traditional self-renewal medium containing LIF-KSR plus FBS, the newly 80 established Adnp-/-ESC colonies overall exhibited typical ESC-like morphology (Fig. 81 1d). To understand how loss of Adnp affected the global gene expression, we 82 performed RNA-sequencing (RNA-seq) experiments for control and early passaged 83Adnp-/-ESCs. Our RNA-seq analysis showed that the primitive endoderm genes such 84 as Gata6, Gata4, Sox17, Sox7 and Sparc were slightly up-regul...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…WISH was performed as described previously 33 . For making the RNA probes, total RNA was extracted from zebrafish embryos, and cDNAs were made by RT-PCR.…”

Section: Methodsmentioning

confidence: 99%

Section: Supplementary Figmentioning

confidence: 99%

See 3 more Smart Citations

ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

Sun

Peng

Cao

et al. 2019

Preprint

Self Cite

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ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

et al. 2020

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ADNP (Activity Dependent Neuroprotective Protein) is a neuroprotective protein whose aberrant expression has been frequently linked to neural developmental disorders, including the Helsmoortel-Van der Aa syndrome (also called the ADNP syndrome). However, its role in neural development and pathology remains unclear. Here, we show that ADNP is required for neural induction and differentiation by enhancing Wnt signaling. Mechanistically, ADNP functions to stabilize β-Catenin through binding to its armadillo domain which prevents its association with key components of the degradation complex: Axin and APC. Loss of ADNP promotes the formation of the degradation complex and β-Catenin degradation via ubiquitinproteasome pathway, resulting in down-regulation of key neuroectoderm developmental genes. In addition, adnp gene disruption in zebrafish leads to defective neurogenesis and reduced Wnt signaling. Our work provides important insights into the role of ADNP in neural development and the pathology of the Helsmoortel-Van der Aa syndrome caused by ADNP gene mutation.

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Epigenetic control of coordinated hematopoietic and cardiovascular development by Rnf2 in zebrafish

Sun

Peng

Feng

2020

Preprint

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Early embryogenesis requires the coordinated development of cardiovascular and hematopoietic lineages. However, the underlying cellular and genetic mechanisms are poorly understood. Here, we show that Rnf2, the core enzymatic component of Polycomb repressive complex 1 (PRC1), plays an important role in the control of cardiovascular and hematopoietic development and differentiation via suppressing the master hematoendothelial progenitor genes in zebrafish. In the absence of Rnf2, a group of transcription factor (TF) genes crucial for hematoendothelial specification such as etv2, gata2, lmo2 and tal1 are significantly up-regulated, which causes an expansion of hematopoietic and endothelial progenitors at the expense of myocardial differentiation, resulting in severe defects in both cardiogenesis and hematopoiesis. Although the number of hematopoietic stem cells (HSCs) is increased, both primitive and definitive waves of hematopoiesis are severely compromised in rnf2 mutant embryos, suggesting that Rnf2 is required for differentiation of blood progenitor cells. Combined ChIP-seq and RNA-seq analysis shows that Rnf2 directly binds to key hematoendothelial progenitor genes and represses its expression. We further show that Rnf2-mediated gene repression depends on its H2Aub1 catalytic activity. We propose that PRC1/Rnf2-mediated epigenetic mechanism plays a key role in coordinated development of cardiovascular and hematopoietic lineages by repressing key hematoendothelial progenitor genes.HighlightsRnf2 is required for suppressing the expression of key hematoendothelial TF genes in precursors and its differentiated descendants.Rnf2 mutant zebrafish embryos display defective hematopoiesis and cardiogenesis.Loss of Rnf2 results in increased HSC numbers and arrested differentiation, hallmarks of leukemia.Rnf2 suppresses hematoendothelial progenitor genes via depositing H2Aub1.

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Mga Modulates Bmpr1a Activity by Antagonizing Bs69 in Zebrafish

Cited by 9 publications

References 39 publications

ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

Epigenetic control of coordinated hematopoietic and cardiovascular development by Rnf2 in zebrafish

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