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

Abstract

Summary:Cranial development is critically influenced by the relative growth of distinct elements. Previous studies have shown that the transcription factor Foxg1 is essential the for development of the 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) depletion on mouse embryos. We report the rapid and complete loss of the telencephalon and cerebellum as well as the 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 before 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 anticleaved caspase 3 and the phosphatidylserine stain PSVue 1 before the near or complete loss of those brain and sensory areas (forebrain, cerebellum, anterior retina, and ear). We conclude that Foxg1-cre-mediated conditional deletion of Dicer1 leads to the absence of functional miRNA followed by complete or nearly complete loss of neurons. Embryonic neurosensory development therefore depends critically on miRNA. Our data further 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.

Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice

“…NeuroVue® dye-coated filter microstrips were cut to appropriately sized pieces using microscissors and inserted into the brainstem and saccule nerve tracts and incubated at 60°C for 4 days. A two-colour tracing system using NeuroVue® Maroon and Red, which have 647-and 568-nm excitation, respectively, was applied [29]. Progression of dye diffusion was monitored using epifluorescent microscopy.…”

Limited inner ear morphogenesis and neurosensory development are possible in the absence of GATA3

“…This is the only other known mutation to completely eliminate cochlear neurosensory development while (Fig. 1D, Kersigo et al, 2011). There is another mutant the Sox2 LCC mouse that displays loss of all cochlear sensory epithelia, but has not been fully investigated with respect to innervation (Kiernan et al, 2005).…”

Evolution and Development of Hair Cell Polarity and Efferent Function in the Inner Ear

“…It should be noted that a series of transformations, from simple concentric arrangements of structures at the apex of a cell to asymmetric specializations of the apical surface, has been proposed for metazoans Brain Behav Evol 2014;83:150-161 DOI: 10.1159/000357752 152 [Fritzsch et al, 2007;Manley and Ladher, 2008] which are likely mediated by genes associated with hair cell development [Duncan and Fritzsch, 2012]: -class A bHLH genes, which regulate neuronal and hair cell differentiation, evolved only in metazoans [Pan et al, 2012]; -approximately 22-nucleotide-long microRNAs, which are essential for neurosensory development [Kersigo et al, 2011], evolved only in metazoans [Pierce et al, 2008] and are highly conserved [Philippe et al, 2011], and -Wnt signaling evolved only in diploblastic organisms [Fairclough et al, 2013]. With the recent finding that Wnt signaling is unique to diploblastic organisms, we explore the link between Wnt signaling and the different aspects of planar cell polarity (PCP).…”