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Article

Developmental Inhibition of Long Intergenic Non-Coding RNA, HOTAIRM1, Impairs Dopamine Neuron Differentiation and Maturation

1
Queensland Centre for Mental Health Research, Wacol, QLD 4076, Australia
2
Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia
3
QIMR Berghofer Medical Research Institute, Herston, QLD 4029, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Yasemin M. Akay
Int. J. Mol. Sci. 2021, 22(14), 7268; https://doi.org/10.3390/ijms22147268
Received: 10 June 2021 / Revised: 1 July 2021 / Accepted: 2 July 2021 / Published: 6 July 2021
(This article belongs to the Special Issue Development of Dopaminergic Neurons)
The dopaminergic (DA) system is important for a range of brain functions and subcortical DA development precedes many cortical maturational processes. The dysfunction of DA systems has been associated with neuropsychiatric disorders such as schizophrenia, depression, and addiction. DA neuron cell fate is controlled by a complex web of transcriptional factors that dictate DA neuron specification, differentiation, and maturation. A growing body of evidence suggests that these transcriptional factors are under the regulation of newly discovered non-coding RNAs. However, with regard to DA neuron development, little is known of the roles of non-coding RNAs. The long non-coding RNA (lncRNA) HOX-antisense intergenic RNA myeloid 1 (HOTAIRM1) is present in adult DA neurons, suggesting it may have a modulatory role in DA systems. Moreover, HOTAIRM1 is involved in the neuronal differentiation in human stem cells suggesting it may also play a role in early DA neuron development. To determine its role in early DA neuron development, we knocked down HOTAIRM1 using RNAi in vitro in a human neuroblastoma cell line, and in vivo in mouse DA progenitors using a novel in utero electroporation technique. HOTAIRM1 inhibition decreased the expression of a range of key DA neuron specification factors and impaired DA neuron differentiation and maturation. These results provide evidence of a functional role for HOTAIRM1 in DA neuron development and differentiation. Understanding of the role of lncRNAs in the development of DA systems may have broader implications for brain development and neurodevelopmental disorders such as schizophrenia. View Full-Text
Keywords: in utero electroporation; lmx1a; Nurr1; tyrosine hydroxylase; mesencephalon in utero electroporation; lmx1a; Nurr1; tyrosine hydroxylase; mesencephalon
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MDPI and ACS Style

Cui, X.; Pertile, R.A.N.; Du, Z.; Wei, W.; Sun, Z.; Eyles, D.W.; Kesby, J.P. Developmental Inhibition of Long Intergenic Non-Coding RNA, HOTAIRM1, Impairs Dopamine Neuron Differentiation and Maturation. Int. J. Mol. Sci. 2021, 22, 7268. https://doi.org/10.3390/ijms22147268

AMA Style

Cui X, Pertile RAN, Du Z, Wei W, Sun Z, Eyles DW, Kesby JP. Developmental Inhibition of Long Intergenic Non-Coding RNA, HOTAIRM1, Impairs Dopamine Neuron Differentiation and Maturation. International Journal of Molecular Sciences. 2021; 22(14):7268. https://doi.org/10.3390/ijms22147268

Chicago/Turabian Style

Cui, Xiaoying, Renata A.N. Pertile, Zilong Du, Wei Wei, Zichun Sun, Darryl W. Eyles, and James P. Kesby. 2021. "Developmental Inhibition of Long Intergenic Non-Coding RNA, HOTAIRM1, Impairs Dopamine Neuron Differentiation and Maturation" International Journal of Molecular Sciences 22, no. 14: 7268. https://doi.org/10.3390/ijms22147268

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