Primary cilia are organelles with a now established role in transducing many canonical developmental signaling pathways. Deficits in ciliary form and/or function lead many human conditions and are collectively called “ciliopathies.” Following the genetics behind a number of our phenotypes has led the Stottmann Lab team into the study of several genes required for normal cilia form and/or function.

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The alien mutation was previously identified in a mutagenesis screen (Herron et al., Nat Genetics 2002). Positional cloning revealed this to be a null mutation in the gene Ttc21b, which is required for protein transport within the primary cilium (Tran et al., Nat Genetics 2008). The alien mutant also has a severe brain patterning defect (Stottmann et al., Dev Biol, 2009). The role of Ttc21b in the developing forebrain and craniofacial tissues, and the role of cilia in development more broadly, is a major focus within the laboratory. One direction of this project is a tissue specific ablation of Ttc21b and other primary cilia genes in the in the developing forebrain and craniofacial tissues.

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Evidence from human genetics studies suggest Ttc21b is a node in a larger ciliary signaling network. The Stottmann Lab team is studying how these genes interact through studies in the mouse and in vitro. The team is also using a forward genetic approach to identify novel loci interacting with Ttc21b in mammalian development and disease and has used a Quantitative Trait Locus analysis to identify a gene it now believes at least partially explains the effects of genetic background on the alien forebrain mutation.