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

Vázquez Echeverría, Citlali

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

Document Type

Doctoral thesis
Published Version

Author

Vázquez Echeverría, Citlali

Director

Pujades, Cristina

Publication Date

2008-12-18

Citation

Vázquez Echeverría, C. Analysis of mouse kreisler mutants reveals new roles of hindbrain-derived signals in the establishment of the otic neurogenic domain. Universitat Pompeu Fabra; 2008. handle: http://hdl.handle.net/10803/7157

This citation was generated automatically.

Doctoral program

Programa de doctorat en Biomedicina

Abstract

The inner ear, the sensory organ responsible for hearing and balance, contains specialized sensory and non-sensory epithelia arranged in a highly complex threedimensional structure. To achieve this complexity, a tight coordination between morphogenesis and cell fate specification is essential during otic development. Tisúes 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 the 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 regionalization, we provide evidence that FGF3 is not sufficient to govern this process. Neither Krox20 nor Fgf3 null mutant embryos, in which Fgf3 is either downregulated or absent in r5 and r6, present ectopic otic 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, and remarkably, 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 a compensatory mechanism between FGFs, and the importance of hindbrain-derived signals in instructing otic patterning and the establishment of the neurogenic domain.

Keywords

hindbrain, inner ear, patterning, labyrinth (ear) - physiology, kreisler/MafB, rhombencephalon, mice as laboratory animals - embriology, developmental neurobiology, laberint (orella) - fisiologia, romboencèfal, ratolins (animals de laboratori) - embriologia, neurobiologia del desenvolupament, FGF, Krox20, neurogenesis