LIN28 alters cell fate succession and acts independently of the <i>let-7</i> microRNA during neurogliogenesis in vitro
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- Erica Balzer
- Department of Molecular Biology, The University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA
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- Christian Heine
- Department of Molecular Biology, The University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA
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- Qiang Jiang
- Division of Developmental Biology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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- Vivian M. Lee
- Division of Developmental Biology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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- Eric G. Moss
- Department of Molecular Biology, The University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA
説明
<jats:p>LIN28 is an RNA-binding protein that is expressed in many developing tissues. It can block let-7 (Mirlet7) microRNA processing and help promote pluripotency. We have observed LIN28 expression in the developing mouse neural tube, colocalizing with SOX2, suggesting a role in neural development. To better understand its normal developmental function, we investigated LIN28 activity during neurogliogenesis in vitro, where the succession of neuronal to glial cell fates occurs as it does in vivo. LIN28 expression was high in undifferentiated cells, and was downregulated rapidly upon differentiation. Constitutive LIN28 expression caused a complete block of gliogenesis and an increase in neurogenesis. LIN28 expression was compatible with neuronal differentiation and did not increase proliferation. LIN28 caused significant changes in gene expression prior to any effect on let-7, notably on Igf2. Furthermore, a mutant LIN28 that permitted let-7 accumulation was still able to completely block gliogenesis. Thus, at least two biological activities of LIN28 are genetically separable and might involve distinct mechanisms. LIN28 can differentially promote and inhibit specific fates and does not function exclusively by blocking let-7 family microRNAs. Importantly, the role of LIN28 in cell fate succession in vertebrate cells is analogous to its activity as a developmental timing regulator in C. elegans.</jats:p>
収録刊行物
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- Development
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Development 137 (6), 891-900, 2010-03-15
The Company of Biologists