title: Mastermind-like 1 (MamL1) and mastermind-like 3 (MamL3) are essential for Notch signaling in vivo.
abstract: Mastermind (Mam) is one of the elements of Notch signaling, a system that plays a pivotal role in metazoan development. Mam proteins form transcriptionally activating complexes with the intracellular domains of Notch, which are generated in response to the ligand-receptor interaction, and CSL DNA-binding proteins. In mammals, three structurally divergent Mam isoforms (MamL1, MamL2 and MamL3) have been identified. There have also been indications that Mam interacts functionally with various other transcription factors, including the p53 tumor suppressor, β-catenin and NF-κB. We have demonstrated previously that disruption of MamL1 causes partial deficiency of Notch signaling in vivo. However, MamL1-deficient mice did not recapitulate total loss of Notch signaling, suggesting that other members could compensate for the loss or that Notch signaling could proceed in the absence of Mam in certain contexts. Here, we report the generation of lines of mice null for MamL3. Although MamL3-null mice showed no apparent abnormalities, mice null for both MamL1 and MamL3 died during the early organogenic period with classic pan-Notch defects. Furthermore, expression of the lunatic fringe gene, which is strictly controlled by Notch signaling in the posterior presomitic mesoderm, was undetectable in this tissue of the double-null embryos. Neither of the single-null embryos exhibited any of these phenotypes. These various roles of the three Mam proteins could be due to their differential physical characteristics and/or their spatiotemporal distributions. These results indicate that engagement of Mam is essential for Notch signaling, and that the three Mam isoforms have distinct roles in vivo.
authors: Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors: Toshinao
authors: T
authors: Oyama
authors: Kenichi
authors: K
authors: Harigaya
authors: Nobuo
authors: N
authors: Sasaki
authors: Yoshiaki
authors: Y
authors: Okamura
authors: Hiroki
authors: H
authors: Kokubo
authors: Yumiko
authors: Y
authors: Saga
authors: Katsuto
authors: K
authors: Hozumi
authors: Akiko
authors: A
authors: Suganami
authors: Yutaka
authors: Y
authors: Tamura
authors: Takahiro
authors: T
authors: Nagase
authors: Hisashi
authors: H
authors: Koga
authors: Motoi
authors: M
authors: Nishimura
authors: Reiko
authors: R
authors: Sakamoto
authors: Mitsuharu
authors: M
authors: Sato
authors: Nobuaki
authors: N
authors: Yoshida
authors: Motoo
authors: M
authors: Kitagawa
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D016695:Glycosyltransferases / Q000378:metabolism; D017403:In Situ Hybridization; D008156:Luciferases; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C467910:MAML3 protein, mouse; C486455:Maml1 protein, mouse; D009687:Nuclear Proteins; D051880:Receptors, Notch; D015534:Trans-Activators; D014157:Transcription Factors; D008156:Luciferases; D016695:Glycosyltransferases; C498392:Lfng protein, mouse