microRNA control of neural progenitor maintenance and specification
Year: 2016
Type: dissertation
Abstract: During neural development, progenitors both divide to expand the neural progenitor (NP) population and differentiate as neurons and glia. This balance of proliferation and differentiation is crucial to the proper development of the central nervous system (CNS). This balance appears to be regulated by multiple different mechanisms including apico-basal polarization by Partitioning defective proteins (Par) as well as Hedgehog signaling, which in addition to its role in dorso-ventral patterning also promotes progenitor proliferation. How both of these pathways are modulated at the end of neurogenesis remains poorly understood. Using bioinformatics we identified the polarity genes pard3 and prkci as candidate targets for microRNA-219 (miR-219). miR-219-deficient zebrafish embryos have a deficit of oligodendrocytes, the myelinating glial cells of the CNS. Because a disruption in polarity could affect the types of cell divisions that NPs undergo, thus altering the balance of cell types that arise, we hypothesized that neural precursor maintenance is regulated by modulation of polarity cues through miR-219. We found that miR-219 inhibited expression of pard3 and prkci mRNAs via target sites in the 3' untranslated region. These data support the role of miR-219 in downregulating expression of Par polarity proteins at the end of neurogenesis. In addition, we also found that Sonic Hedgehog (Shh) signaling was significantly increased in miR-219 morphants, suggesting a role for miR-219 in regulating the levels of Shh. Using prkci mutant zebrafish embryos we found that reduction of apical Par proteins results in a reduction of Shh signaling. These data provide evidence for a new mechanism of NP regulation, in which miR-219 downregulates apical Par proteins and Shh at the end of neurogenesis.
DOI: 10.25677/7gj4-zq41
Author: Hudish, Laura Ioana
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2593151848