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Published on: January 4, 2017
Analysis of Meis2 knockout mice reveals Sonic hedgehog-mediated patterning of the cochlear duct
Hei Yeun Koo1,2, Jae Hwan Oh1,2, María Beatriz Durán Alonso3
1Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea.
Background:
The mechanisms underlying the formation of complex structures such as during the outgrowth of the cochlear duct are still poorly understood.
Results:
We have analyzed the morphological and molecular changes associated with cochlear development in mouse mutants for the transcription factor Meis2, which show defective coiling of the cochlea. These morphological abnormalities were accompanied by the formation of ectopic and extra rows of sensory hair cells. Gene profiling of otic vesicles from Meis2 mutants revealed a dysregulation of genes that are potentially involved in Sonic hedgehog (Shh)-mediated patterning of the cochlear duct. Like in Shh mutants, Meis2 defective mice showed a loss of genes that are expressed in the apical part of the cochlear duct.
Conclusions:
Taken together, these data reveal that the loss of Meis2 leads to a phenotype that resembles Shh mutants, suggesting that Meis2 is instrumental for cochlear Shh signaling. The modulation of the same subset of genes provides an interesting insight into which Shh responsive genes are essential for outgrowth and patterning of the cochlear duct.
Insights
The transcription factor Meis2 is crucial for cochlear duct development and patterning. Loss of Meis2 disrupts cochlear coiling and resembles Sonic hedgehog (Shh) signaling defects.
Area of Science:
- Developmental biology
- Genetics
- Otolaryngology
Background:
- Cochlear duct formation mechanisms remain poorly understood.
- Complex structure development requires precise genetic regulation.
- Transcription factors play key roles in embryonic development.
Purpose of the Study:
- Investigate the role of transcription factor Meis2 in cochlear development.
- Analyze morphological and molecular changes in Meis2 mutant mice.
- Elucidate the relationship between Meis2 and Sonic hedgehog (Shh) signaling in the cochlea.
Main Methods:
- Analysis of morphological changes in mouse cochlear development.
- Gene profiling of otic vesicles from Meis2 mutant mice.
- Comparison of Meis2 mutant phenotypes with Shh mutant phenotypes.
Main Results:
- Meis2 mutants exhibit defective cochlear coiling and abnormal sensory hair cell formation.
- Gene expression profiling reveals dysregulation of Shh-mediated patterning genes in Meis2 mutants.
- Meis2 deficiency leads to a loss of genes in the apical cochlear duct, similar to Shh mutants.
Conclusions:
- Loss of Meis2 results in a phenotype resembling Shh mutants, indicating Meis2 is essential for cochlear Shh signaling.
- Meis2 plays a critical role in the outgrowth and patterning of the cochlear duct.
- The study provides insights into Shh-responsive genes vital for cochlear development.
