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Updated: Oct 2, 2026

Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates
Published on: April 22, 2019
NF1 tumor suppressor mRNA is targeted to the cell-cell contact zone in Ca(2+)-induced keratinocyte differentiation
Heli Ylä-Outinen1, Jussi Koivunen, Marja Nissinen
1Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland.
Summary:
We have previously shown that NF1 (type 1 neurofibromatosis) p21ras GTPase-activating tumor suppressor protein undergoes major relocalization during the formation of cell-cell junctions in differentiating keratinocytes in vitro. This prompted us to study the distribution of NF1 mRNA under the same conditions by in situ hybridization. In differentiating keratinocytes, the NF1 mRNA signal intensified within the cell cytoplasm within the first 0.5 to 2 hours after induction of cellular differentiation. First, the hybridization signal was evenly distributed throughout the cytoplasm. Subsequently, NF1 mRNA was gradually polarized to the cellular periphery at the side of cell-cell junctions and finally disappeared. Reappearance of NF1 mRNA was found in migrating keratinocytes forming a bilayered culture. Disruption of microfibrillar cytoskeleton, but not microtubules, caused a marked change in the subcellular distribution of NF1 mRNA. This data may suggest that intact actin microfilaments are essential for transport of NF1 mRNA to the cell periphery. This is the first study demonstrating that NF1, or any tumor suppressor mRNA, belongs to a rare group of mRNAs not targeted to free polysomes or ribosomes of the rough endoplasmic reticulum. This finding recognizes a potential way for post-transcriptional modification of NF1 expression.
Insights
Neurofibromatosis type 1 (NF1) mRNA relocates in differentiating skin cells, suggesting actin microfilaments are key for its transport. This finding reveals a novel mechanism for regulating NF1 expression.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Type 1 neurofibromatosis (NF1) is a genetic disorder.
- NF1 tumor suppressor protein relocalizes during keratinocyte differentiation.
- The distribution of NF1 mRNA during this process was previously unknown.
Purpose of the Study:
- To investigate the subcellular localization of NF1 mRNA in differentiating keratinocytes.
- To determine the role of the cytoskeleton in NF1 mRNA distribution.
- To explore potential post-transcriptional regulation of NF1.
Main Methods:
- In situ hybridization to detect NF1 mRNA.
- Induction of keratinocyte differentiation in vitro.
- Disruption of the microfibrillar cytoskeleton and microtubules.
Main Results:
- NF1 mRNA signal intensified and polarized to cell junctions in differentiating keratinocytes.
- NF1 mRNA disappeared from junctions and reappeared in migrating cells.
- Disruption of actin microfilaments, but not microtubules, altered NF1 mRNA distribution.
- NF1 mRNA is not targeted to free polysomes or the rough endoplasmic reticulum.
Conclusions:
- Actin microfilaments are essential for the peripheral transport of NF1 mRNA.
- NF1 mRNA exhibits unique localization patterns, distinct from mRNAs targeted to ribosomes.
- This suggests a novel mechanism for post-transcriptional regulation of NF1 expression.
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