The lung is one of the most morphologically diverse organs among vertebrate species. Phylogenetically, much of this diversity appears to arise from the way epithelial tubes branch and change shape ranging from very saccular to highly branched structures. We are interested in understanding the genetic mechanisms that underlie this range in morphology. Fgf10 signaling has been demonstrated to play a critical role in regulating whether the lung epithelium undergoes branching morphogenesis (through low, graded levels of Fgf10) or forms sacs (high, uniform exposure to Fgf10). We hypothesize therefore that interspecies differences in Fgf10 expression may be a mechanism to underlie morphological diversity that exists in the vertebrate lung. To test this hypothesis, we have been performing enhancer swap experiments taking reptilian Fgf10 enhancers and knocking them into orthologous loci in the genome of chicken primordial germ cells (cPGCs). These targeted cPGCs are introduced into the gonad of developing chicken embryos where they will ultimately develop into germ cells in the adult chicken. These germ line chimeras can then be bred to generate fully transgenic chicks to determine if enhancer swaps are sufficient to drive a reptilian pattern of lung morphogenesis in an avian. I will discuss the gene editing approaches my laboratory is taking to knock in reptilian Fgf10 enhancers into the orthologous locus in in the chicken.
Support or Funding Information
Altering the Chicken Genome: A Novel Tool to Impact Biomedical and Poultry Science. Turkey Vaccine Grant (Brigham Young University).
lt;igt;Altering the Chicken Genome: A Novel Tool to Impact Biomedical and Poultry Science.lt;/igt; Turkey Vaccine Grant (Brigham Young University).
