MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary
Abstract
The midbrain-hindbrain boundary (MHB) is a long-lasting organizing center in the vertebrate neural tube that is both necessary and sufficient for the ordered development of midbrain and anterior hindbrain (midbrain-hindbrain domain, MH). The MHB also coincides with a pool of progenitor cells that contributes neurons to the entire MH. Here we show that the organizing activity and progenitor state of the MHB are co-regulated by a single microRNA, miR-9, during late embryonic development in zebrafish. Endogenous miR-9 expression, initiated at late stages, selectively spares the MHB. Gain- and loss-of-function studies, in silico predictions and sensor assays in vivo demonstrate that miR-9 targets several components of the Fgf signaling pathway, thereby delimiting the organizing activity of the MHB. In addition, miR-9 promotes progression of neurogenesis in the MH, defining the MHB progenitor pool. Together, these findings highlight a previously unknown mechanism by which a single microRNA fine-tunes late MHB coherence via its co-regulation of patterning activities and neurogenesis.
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The physiological importance of miRNAs in nervous system functions and disease states has been suggested by previous studies of a small number of brain-enriched miRNAs.
“The physiological importance of miRNAs in nervous system functions and disease states has also been suggested by previous studies of a small number of brainenriched miRNAs (Leucht et al., 2008;Mellios et al., 2008;Packer et al., 2008;Cheng et al., 2009;Schratt, 2009).”
From Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes (2013) · cites this paper as Leucht et al., 2008
MiR-9 is expressed in the developing embryonic CNS, is highly conserved, and facilitates neurogenesis and differentiation.
“MiR-9, which is expressed in the developing embryonic CNS, is highly conserved and facilitates neurogenesis and differentiation [45–48].”
From Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression (2022) · cites this paper as [47]
In zebrafish, miR-9 is important for midbrain-hindbrain boundary definition.
“In zebrafish, miR-9 is important midbrain-hindbrain boundary definition (Leucht et al., 2008).”
From The Bifunctional microRNA miR-9/miR-9* Regulates REST and CoREST and Is Downregulated in Huntington's Disease (2008) · cites this paper as Leucht et al., 2008
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“miR-9 was also predicted to target human, mouse and chicken Hes1 (data not shown), which maintains progenitor pool”
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Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression
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The Brain-Enriched MicroRNA miR-9-3p Regulates Synaptic Plasticity and Memory
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- Authors
- Leucht, C., Stigloher, C., Wizenmann, A., Klafke, R., Folchert, A., & Bally-Cuif, L.
- Venue
- Nature Neuroscience
- Published
- 2008-05-04
- Volume
- 11
- Issue
- 6
- Pages
- 641-648
- ISSN
- 1097-6256
- 1546-1726
- Cited by
- 270
- References
- 3
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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