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 D. Gray, Garrett Soukup, Bernd Fritzsch

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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® 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.

Original languageEnglish
Pages (from-to)326-341
Number of pages16
JournalGenesis
Volume49
Issue number4
DOIs
StatePublished - Apr 2011

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Prosencephalon
MicroRNAs
Ear
Telencephalon
Cerebellum
Nerve Tissue
Olfactory Mucosa
Phosphatidylserines
Brain
Growth
Skull
Caspase 3
Embryonic Development
Retina
Transcription Factors
Coloring Agents
Embryonic Structures
Neurons

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Cell Biology
  • Genetics

Cite this

The role of sensory organs and the forebrain for the development of the craniofacial shape as revealed by Foxg1-cre-mediated microRNA loss. / Kersigo, Jennifer; D'Angelo, Alex; Gray, Brian D.; Soukup, Garrett; Fritzsch, Bernd.

In: Genesis, Vol. 49, No. 4, 04.2011, p. 326-341.

Research output: Contribution to journalArticle

Kersigo, Jennifer ; D'Angelo, Alex ; Gray, Brian D. ; Soukup, Garrett ; Fritzsch, Bernd. / The role of sensory organs and the forebrain for the development of the craniofacial shape as revealed by Foxg1-cre-mediated microRNA loss. In: Genesis. 2011 ; Vol. 49, No. 4. pp. 326-341.
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