Austin Lam, MD

Genotype-phenotype correlation of tracheal cartilaginous sleeves and Fgfr2 mutations in mice

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Jenny Stone says:

June 17, 2020 at 3:46 am

Very interesting study! The mutant phenotype in Fig 4 reminds me of what is seen in lateral line neuromast development when FGF signaling is disrupted. Several other signaling pathways have been implicated in the process of neuromast migration, deposition and consolidation, including Notch, Wnt, and certain cytokines. I wonder if these same pathways are dysregulated in your mutants.

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1. Austin Lam says:
  
  June 17, 2020 at 2:52 pm
  
  Thanks for the comment, Dr. Stone!
  Unfortunately, very little is known about the pathophysiologic mechanism of TCS. Actually, one of our plans for future work is to evaluate which pathways are involved human chondrocytes with these FGFR2 mutations.
  
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Jake Dahl says:

June 17, 2020 at 4:51 pm

Dr. Cunningham has human mesenchymal stem cell lines derived from patients with specific FGFR mutations. We plan to use these lines to further investigate which signaling pathway(s) are involved with TCS formation. We are also in the process of obtaining FGFR2 C342Y mice at SCH to look at the airway development at specific embryologic time points. We are also in the process of creating a FGFR2 W290C knock in mouse line as this genotype has the best correlation with the TCS phenotype in humans.

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