PMID- 26519518
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151116
LR  - 20181113
IS  - 2046-6390 (Print)
IS  - 2046-6390 (Electronic)
IS  - 2046-6390 (Linking)
VI  - 4
IP  - 11
DP  - 2015 Oct 30
TI  - Mindbomb 2 is dispensable for embryonic development and Notch signalling in 
      zebrafish.
PG  - 1576-82
LID - 10.1242/bio.014225 [doi]
AB  - 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 mib(tfi91)-null phenotypes nor did it alleviate antimorphic mib(ta52b) 
      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.
CI  - (c) 2015. Published by The Company of Biologists Ltd.
FAU - Mikami, Shohei
AU  - Mikami S
AD  - Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, 
      Japan.
FAU - Nakaura, Mizuki
AU  - Nakaura M
AD  - Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, 
      Japan.
FAU - Kawahara, Atsuo
AU  - Kawahara A
AD  - Laboratory for Developmental Biology, Center for Medical Education and Sciences, 
      Graduate School of Medical Science, University of Yamanashi, Yamanashi 409-3898, 
      Japan.
FAU - Mizoguchi, Takamasa
AU  - Mizoguchi T
AD  - Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, 
      Japan.
FAU - Itoh, Motoyuki
AU  - Itoh M
AD  - Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, 
      Japan mito@chiba-u.jp.
LA  - eng
PT  - Journal Article
DEP - 20151030
PL  - England
TA  - Biol Open
JT  - Biology open
JID - 101578018
PMC - PMC4728363
OTO - NOTNLM
OT  - Mib2
OT  - Neuronal development
OT  - Notch signalling
OT  - Ubiquitin ligase
OT  - Zebrafish
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2015/11/01 06:00
MHDA- 2015/11/01 06:01
PMCR- 2015/10/30
CRDT- 2015/11/01 06:00
PHST- 2015/11/01 06:00 [entrez]
PHST- 2015/11/01 06:00 [pubmed]
PHST- 2015/11/01 06:01 [medline]
PHST- 2015/10/30 00:00 [pmc-release]
AID - bio.014225 [pii]
AID - BIO014225 [pii]
AID - 10.1242/bio.014225 [doi]
PST - epublish
SO  - Biol Open. 2015 Oct 30;4(11):1576-82. doi: 10.1242/bio.014225.