title: Functional dicer is necessary for appropriate specification of radial glia during early development of mouse telencephalon.
abstract: Early telencephalic development involves transformation of neuroepithelial stem cells into radial glia, which are themselves neuronal progenitors, around the time when the tissue begins to generate postmitotic neurons. To achieve this transformation, radial precursors express a specific combination of proteins. We investigate the hypothesis that micro RNAs regulate the ability of the early telencephalic progenitors to establish radial glia. We ablate functional Dicer, which is required for the generation of mature micro RNAs, by conditionally mutating the Dicer1 gene in the early embryonic telencephalon and analyse the molecular specification of radial glia as well as their progeny, namely postmitotic neurons and basal progenitors. Conditional mutation of Dicer1 from the telencephalon at around embryonic day 8 does not prevent morphological development of radial glia, but their expression of Nestin, Sox9, and ErbB2 is abnormally low. The population of basal progenitors, which are generated by the radial glia, is disorganised and expanded in Dicer1⁻/⁻ dorsal telencephalon. While the proportion of cells expressing markers of postmitotic neurons is unchanged, their laminar organisation in the telencephalic wall is disrupted suggesting a defect in radial glial guided migration. We found that the laminar disruption could not be accounted for by a reduction of the population of Cajal Retzius neurons. Together, our data suggest novel roles for micro RNAs during early development of progenitor cells in the embryonic telencephalon.
authors.affiliation: Developmental Biology Laboratory, Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom. t.nowakowski@sms.ed.ac.uk
authors.forename: Tomasz Jan
authors.initials: TJ
authors.lastname: Nowakowski
authors.forename: Karolina Sandra
authors.initials: KS
authors.lastname: Mysiak
authors.forename: Thomas
authors.initials: T
authors.lastname: Pratt
authors.forename: David Jonathan
authors.initials: DJ
authors.lastname: Price
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013687:Telencephalon / Q000196:embryology* / Q000378:metabolism*
chemical_list: D053487:DEAD-box RNA Helicases; D007381:Intermediate Filament Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D064231:Nestin; D018719:Erb-b2 Receptor Tyrosine Kinases; D043244:Ribonuclease III; D055758:SOX9 Transcription Factor; C577485:Nes protein, mouse; C527933:Sox9 protein, mouse; C524056:Erbb2 protein, mouse; C509781:Dicer1 protein, mouse