The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway
Open accessAbstract
MACF1 (microtubule actin cross-linking factor 1) is a multidomain protein that can associate with microfilaments and microtubules. We found that MACF1 was highly expressed in neuronal tissues and the foregut of embryonic day 8.5 (E8.5) embryos and the head fold and primitive streak of E7.5 embryos. MACF1 −/− mice died at the gastrulation stage and displayed developmental retardation at E7.5 with defects in the formation of the primitive streak, node, and mesoderm. This phenotype was similar to Wnt-3 −/− and LRP5/6 double-knockout embryos. In the absence of Wnt, MACF1 associated with a complex that contained Axin, β-catenin, GSK3β, and APC. Upon Wnt stimulation, MACF1 appeared to be involved in the translocation and subsequent binding of the Axin complex to LRP6 at the cell membrane. Reduction of MACF1 with small interfering RNA decreased the amount of β-catenin in the nucleus, and led to an inhibition of Wnt-induced TCF/β-catenin-dependent transcriptional activation. Similar results were obtained with a dominant-negative MACF1 construct that contained the Axin-binding region. Reduction of MACF1 in Wnt-1-expressing P19 cells resulted in decreased T ( Brachyury ) gene expression, a DNA-binding transcription factor that is a direct target of Wnt/β-catenin signaling and required for mesoderm formation. These results suggest a new role of MACF1 in the Wnt signaling pathway.
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PAX5 and FEZF2 are involved in transcription regulation during central nervous system development.
“PAX5 and FEZF2 are involved in transcription regulation during central nervous system development.4,24,37”
From Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes (2019) · cites this paper as [24]
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References 41 · Cited by 191
- Authors
- Chen, H.-J., Lin, C.-M., Lin, C.-S., Perez-Olle, R., Leung, C. L., & Liem, R. K. H.
- Affiliations
- Columbia University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-06-30
- Volume
- 20
- Issue
- 14
- Pages
- 1933-1945
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1522081
- OpenAlex
- W1984489797
- Cited by
- 191
- References
- 41
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 8 · 2023: 5 · 2022: 5 · 2021: 10 · 2020: 7 · 2019: 8 · 2018: 12 · 2017: 22 · 2016: 13 · 2015: 10 · 2014: 11 · 2013: 11 · 2012: 8
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Muscular Dystrophy Association
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Keywords
- MACF1, Wnt signaling, β-catenin, Axin, LRP6, GSK3β, APC, mesoderm formation, primitive streak, gastrulation, Brachyury, embryonic development
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Dystonin, Animals, Base Sequence, Carrier Proteins, Cell Membrane, Cytoskeletal Proteins, Mesoderm, Microfilament Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Repressor Proteins, Signal Transduction, Protein Structure, Tertiary, Mice, Knockout, Gene Expression Regulation, Developmental, Protein Transport, Adenomatous Polyposis Coli Protein, Glycogen Synthase Kinase 3, Multiprotein Complexes, Wnt Proteins, beta Catenin, Mice, Axin Protein
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