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The role of sensory organs and the forebrain for the development of the craniofacial shape as revealed by Foxg1-cre mediated microRNA loss
Journal article   Open access

The role of sensory organs and the forebrain for the development of the craniofacial shape as revealed by Foxg1-cre mediated microRNA loss

Jennifer Kersigo, Alex D’Angelo, Brian Gray, Garrett A Soukup and Bernd Fritzsch
Genesis (New York, N.Y. : 2000), Vol.49(4), pp.326-341
04/2011
DOI: 10.1002/dvg.20714
PMCID: PMC3079063
PMID: 21225654
url
https://doi.org/10.1002/dvg.20714View
Published (Version of record) Open Access

Abstract

Cranial development is critically influenced by the relative growth of distinct elements. Previous studies have shown the transcription factor Foxg1 to be expressed is essential for development of telencephalon, olfactory epithelium, parts of the eye and the ear. Here we investigate the effects of a Foxg1-cre mediated conditional deletion of Dicer1 and microRNA (miRNA) on mouse embryos. We report the rapid and complete loss of the telencephalon and cerebellum as well as severe reduction in the ears and loss of the anterior half of the eyes. These losses result in unexpectedly limited malformations of anterodorsal aspects of the skull. We investigated the progressive disappearance of these initially developing structures and found a specific miRNA of nervous tissue, miR-124, to disappear prior to reduction in growth of the specific neurosensory areas. Correlated with the absence of miR-124, these areas showed numerous apoptotic cells that stained positive for anti-cleaved caspase 3 and the phosphatidylserine stain PSVue prior to the near or complete loss of those brain and sensory areas (forebrain, cerebellum, anterior retina, ear). We conclude that Foxg1-cre mediated conditional deletion of Dicer1 leads to absence of functional miRNA followed by complete or nearly complete loss of neurons. Embryonic neurosensory development therefore depends critically on miRNA. Our data suggest that loss of a given neuronal compartment can be triggered using early deletion of Dicer1 and thus provides a novel means to genetically remove specific neurosensory areas to investigate loss of their function on morphology (this study) or signal processing within the brain.
eye conditional deletion forebrain cerebellum ear cre

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