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Developmental Biology
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Developmental Biology
Article . 2008
License: Elsevier Non-Commercial
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Developmental Biology
Article . 2008 . Peer-reviewed
License: Elsevier Non-Commercial
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Analysis of mouse kreisler mutants reveals new roles of hindbrain-derived signals in the establishment of the otic neurogenic domain

Authors: Vázquez-Echeverría, Citlali; Dominguez-Frutos, Elena; Charnay, Patrick; Schimmang, Thomas; Pujades, Cristina;

Analysis of mouse kreisler mutants reveals new roles of hindbrain-derived signals in the establishment of the otic neurogenic domain

Abstract

The inner ear, the sensory organ responsible for hearing and balance, contains specialized sensory and non-sensory epithelia arranged in a highly complex three-dimensional structure. To achieve this complexity, a tight coordination between morphogenesis and cell fate specification is essential during otic development. Tissues surrounding the otic primordium, and more particularly the adjacent segmented hindbrain, have been implicated in specifying structures along the anteroposterior and dorsoventral axes of the inner ear. In this work we have first characterized the generation and axial specification of the otic neurogenic domain, and second, we have investigated the effects of the mutation of kreisler/MafB--a gene transiently expressed in rhombomeres 5 and 6 of the developing hindbrain--in early otic patterning and cell specification. We show that kr/kr embryos display an expansion of the otic neurogenic domain, due to defects in otic patterning. Although many reports have pointed to the role of FGF3 in otic regionalisation, we provide evidence that FGF3 is not sufficient to govern this process. Neither Krox20 nor Fgf3 mutant embryos, characterized by a downregulation or absence of Fgf3 in r5 and r6, display ectopic neuroblasts in the otic primordium. However, Fgf3-/-Fgf10-/- double mutants show a phenotype very similar to kr/kr embryos: they present ectopic neuroblasts along the AP and DV otic axes. Finally, partial rescue of the kr/kr phenotype is obtained when Fgf3 or Fgf10 are ectopically expressed in the hindbrain of kr/kr embryos. These results highlight the importance of hindbrain-derived signals in the regulation of otic neurogenesis.

Keywords

Male, Neurogenesis, Fibroblast Growth Factor 3, Apoptosis, Mice, Inner ear, Morphogenesis, FGF, Animals, Molecular Biology, Early Growth Response Protein 2, Cell Proliferation, Mice, Knockout, Neurons, kreisler/MafB, Cell Biology, Hindbrain, Mice, Mutant Strains, Patterning, Rhombencephalon, Phenotype, Ear, Inner, Female, Krox20, Fibroblast Growth Factor 10, Developmental Biology, Signal Transduction

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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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