Targeted disruption of <i>Mib2</i> causes exencephaly with a variable penetrance

Wu, Jiang; Rajendra, Rashmi; Barsi, Julius C.; Durfee, Larissa A.; Benito, Eva; Gao, Guang; Kuruvilla, Mariam; Hrdličková, Radmila; Liss, Andrew S.; Artzt, Karen

doi:10.1002/dvg.20349

Cited by 13 publications

(12 citation statements)

References 14 publications

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“…Here, we show that Mib2 is dispensable, at least during neurogenesis, somitogenesis, and pigment cell development, and for Notch signalling in zebrafish. Similar observations have been made in the mouse and Drosophila ( Koo et al, 2007 ; Nguyen et al, 2007 ; Wu et al, 2007 ). Furthermore, our data suggest that the maternal gene product of Mib2 does not play a critical role during zebrafish development.…”

Section: Discussionsupporting

confidence: 85%

Mindbomb 2 is dispensable for embryonic development and Notch signalling in zebrafish

et al. 2015

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The Mindbomb E3 ubiquitin protein ligase (Mib) family of proteins, Mib1 and Mib2, are RING finger ubiquitin ligases that share specific substrates. Mib1 is known to play essential roles in Notch signalling by ubiquitinating Notch ligands in vivo. Conversely, the functions of Mib2 in vivo are not fully understood, although Mib2 ubiquitinates multiple substrates, including Notch ligands, in vitro. To determine the Notch-dependent and Notch-independent functions of Mib2 in vivo, we generated mutant alleles of zebrafish mib2 using transcription activator-like effector nucleases (TALENs). We found that mib2 homozygous mutants were viable and fertile. Notch-mediated functions, such as early neurogenesis, somitogenesis, and pigment cell development, were not affected in mib2 mutant embryos. The lack of Notch-deficient phenotypes in mib2 mutants was not due to compensation by a mib2 maternal gene product because mib2 maternal-zygotic mutants also did not exhibit a distinct phenotype. We also showed that Mib2 does not redundantly act with Mib1 because the genetic ablation of mib2 neither enhanced mibtfi91-null phenotypes nor did it alleviate antimorphic mibta52b phenotypes. Furthermore, the postulated Notch-independent roles of Mib2 in maintaining muscular integrity and N-methyl-D-aspartate receptor (NMDAR) activity were not evident: mib2 mutants did not show phenotypes different from that of the control embryos. These observations suggest that Mib2 is dispensable for embryonic development and does not have redundant functions with Mib1 in Notch signalling at least during early development stages in zebrafish.

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Section: Discussionsupporting

confidence: 85%

Mindbomb 2 is dispensable for embryonic development and Notch signalling in zebrafish

et al. 2015

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“…MIB1 is constitutively and ubiquitously expressed in both embryo and adult tissues, whereas MIB2 is primarily found in some adult tissues (Koo et al, 2005b). Consequently, MIB2-deficient mice do not share the same developmental defects noted for MIB1-deficient animals (Koo et al, 2007; Wu et al, 2007). …”

Section: Discussionmentioning

confidence: 94%

Mapping a Dynamic Innate Immunity Protein Interaction Network Regulating Type I Interferon Production

et al. 2011

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SUMMARY To systematically investigate innate immune signaling networks regulating production of type I interferon, we analyzed protein complexes formed after microbial recognition. Fifty-eight baits were associated with 260 interacting proteins forming a human innate immunity interactome for type I interferon (HI5) of 401 unique interactions; 21% of interactions were modulated by RNA, DNA, or LPS. Overexpression and depletion analyses identified 22 unique genes that regulated NF-κB and ISRE reporter activity, viral replication, or virus-induced interferon production. Detailed mechanistic analysis defined a role for mind bomb (MIB) E3 ligases in K63-linked ubiquitination of TBK1, a kinase that phosphorylates IRF transcription factors controlling interferon production. Mib genes selectively controlled responses to cytosolic RNA. MIB deficiency reduced antiviral activity, establishing the role of MIB proteins as positive regulators of antiviral responses. The HI5 provides a dynamic physical and regulatory network that serves as a resource for mechanistic analysis of innate immune signaling.

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“…The genes, which encode and disrupt NTDs, include Hectd1, Mib2 and Smurf1/2. There is a strong implication that these proteins function as signaling the foliate metabolism pathways for neural tube closure [12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Study of Neural Tube Defects in 1000 Foetuses With Clinical Spectrum

Himabindu¹,

Anjum²,

Saritha³

et al. 2015

IJAR

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A variety of malformations are included under the description of Neural tube defects (NTDs). These are abnormalities of the embryonic neuralization process. The congenital malformations of human structure and are of great interest to anatomists, obstetricians, pediatricians and radiologists. NTDs are among the commonest and most severe disorders, affecting 0.5-2 per 1000 established pregnancies, and are second commonest group of birth defects, after congenital heart defects. A valuable contribution of this study, the neural tube defects aimed at clinical methods and refined for the prenatal diagnosis in utero. Materials and Methods: This comprehensive study was undertaken to know the incidence of detail knowledge of neural tube defects in KIMS Narketpally and KAMS & RC Hyderabad, among 1000 births during the period of two years. We found seven fetuses with neural tube defects involving brain and spinal cord. A detailed study was done emphasizing on embryology and genetic and non-genetic concepts. Results & Conclusion: The seven fetuses were stillbirths and aborted babies between 20 to 40 weeks, presented with neural tube defects (0.7%). Five fetuses were females and two fetuses were males. The spinal defects were 0.4%, cranial defects 0.2% and complete neural tube defects is 0.1%. This review article discusses the classification, clinical research and epidemiological understanding of NTDs and correlated with the available literatures.

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Targeted disruption of Mib2 causes exencephaly with a variable penetrance

Cited by 13 publications

References 14 publications

Mindbomb 2 is dispensable for embryonic development and Notch signalling in zebrafish

Mindbomb 2 is dispensable for embryonic development and Notch signalling in zebrafish

Mapping a Dynamic Innate Immunity Protein Interaction Network Regulating Type I Interferon Production

Comprehensive Study of Neural Tube Defects in 1000 Foetuses With Clinical Spectrum

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