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Tooth morphogenesis and ameloblast differentiation are regulated by micro-RNAs
Frederic Michon1, Mark Tummers, Marika Kyyrönen
1Institute of Biotechnology, Developmental Biology Program, PO Box 56, University of Helsinki, FIN-00014, Helsinki, Finland. Frederic.Michon@helsinki.fi
Developmental Biology
|January 28, 2010
Summary
MicroRNAs (miRNAs) are crucial for tooth development, regulating shape and enamel formation. This study reveals their role in fine-tuning signaling pathways, impacting tooth evolution.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Tooth morphogenesis is regulated by ectodermal signaling pathways.
- The role of micro-RNA (miRNA) in tooth development (odontogenesis) remains largely unknown.
- RNA interference (RNAi) pathway effectors show dynamic expression during tooth development.
Purpose of the Study:
- To investigate the function of miRNAs in tooth morphogenesis and dental cell differentiation.
- To identify specific miRNAs involved in tooth development and their target genes.
- To understand the role of miRNAs in regulating conserved signaling networks during odontogenesis.
Main Methods:
- Microarray profiling to identify tooth-enriched miRNAs during morphogenesis and in the stem cell niche.
- Conditional deletion of Dicer-1 in the dental epithelium (Dcr(K14)(-)(/)(-)) to assess miRNA pathway function.
- Construction of a novel ectodermal organ-oriented database (miRTooth) for target gene prediction.
Main Results:
- Conditional deletion of Dicer-1 led to significant tooth shape aberrations and impaired enamel formation.
- Observed cusp patterns in mutants resembled ancestral rodents and mouse models with altered signaling.
- Ectopic epithelial budding in incisors and impaired ameloblast differentiation were noted.
- Predicted miRNA targets included key components of morphogenetic signaling pathways.
Conclusions:
- MicroRNAs fine-tune conserved signaling networks, significantly modulating tooth morphogenesis.
- miRNAs likely played a critical role in the evolutionary history of teeth.
- The miRTooth database aids in identifying miRNA targets in ectodermal organ development.
Related Concept Videos
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
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