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Fgf8 and Fgf3 are required for zebrafish ear placode induction, maintenance and inner ear patterning
1Max-Planck-Institute of Molecular Cell Biology and Genetics (Dresden), Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Mechanisms of Development
|October 19, 2002
Summary
Fibroblast growth factor 8 (Fgf8) and Fgf3 are crucial for inner ear development in vertebrates. These signaling molecules regulate otic placode formation, maintenance, and patterning, ensuring proper hearing and balance organ development.
Area of Science:
- Developmental Biology
- Genetics
- Neuroscience
Background:
- The vertebrate inner ear, essential for hearing and equilibrium, develops from simple ectodermal structures.
- Genetic mechanisms governing inner ear development are not fully understood.
- Fibroblast growth factors (Fgfs) and Wnt proteins are implicated in otic placode induction.
Purpose of the Study:
- Investigate the role of Fgf8, a hindbrain-derived signal, in conjunction with Fgf3 during inner ear development.
- Elucidate the genetic control of otic placode induction, maintenance, and otic vesicle patterning.
- Determine the specific contributions of Fgf3 and Fgf8 to inner ear formation.
Main Methods:
- Utilized the acerebellar (ace) mutant, which has a non-functional Fgf8 product.
- Employed gene expression markers to assess otic placode formation and maintenance.
- Performed misexpression studies with fgf8 and Fgf8-coated beads.
- Conducted cell transplantation experiments and expression analysis.
- Used antisense-morpholino injection to inactivate Fgf3 and Fgf8.
- Studied mzoep mutant embryos to assess the role of endomesoderm.
Main Results:
- Homozygous ace/fgf8 mutants exhibit smaller ears, abnormal structures, and behavioral defects.
- Fgf8 and Fgf-signaling are essential for normal otic placode formation and maintenance.
- Misexpression of fgf8 can enhance ear size and marker gene expression.
- Fgf8 is required in the hindbrain (rhombomere 4-6) for placode development.
- Joint inactivation of Fgf3 and Fgf8 leads to ear-less embryos.
- Fgfs play roles in both early induction and later differentiation of inner ear structures and mechanosensory hair cells.
- Endomesoderm influences the spatial restriction of placode development.
Conclusions:
- Fgf3 and Fgf8 act synergistically during otic placode induction and differentiation.
- Fgfs have independent functions in later otic vesicle and lateral line organ development.
- A model for zebrafish inner ear development involving sequential Fgf signaling is proposed.