Cilia are microtubule based structures that can be motile or immotile, the latter being referred to as primary cilia. In contrast to motile cilia, such as those found on epithelia of the trachea, the importance of the primary cilium is relatively undefined despite their presence on most mammalian cells. Cilia are extremely complex organelles which are devoid of ribosomes, thus, proteins required for cilia assembly, maintenance, and signaling must be imported into the cilium. This occurs through a microtubule-based transport system called intraflagellar transport (IFT). Proteins involved in IFT concentrate around the basal body at the base of the cilium and assemble into complexes (IFT particles) which are moved up the cilium by a kinesin and returned by a cytoplasmic dynein. The IFT particle is thought to mediate the transport of cargo into the cilium as well as to deliver signals initiated in the cilium to the cytosol. Although the primary cilium was once thought to be a vestigial organelle, recent studies have uncovered that cilia in mammals are required for viability and that dysfunction of the cilium is associated with a large number of developmental abnormalities and disease phenotypes. This now includes obesity, cystic kidney, liver, and pancreatic diseases, hydrocephalus, skin and hair follicle abnormalities, random left-right body access specification, and skeletal defects. Although studies in mice and humans now indicate that cilia are critically important organelles, the functions of cilia and the pathways in which they are required remains largely unknown. Addressing these issues is the major focus of my group’s research. Our studies utilize comparative approaches in both mouse and C. elegans to investigate four major interrelated themes: 1) What roles do cilia play in regulating signaling pathways? 2) What are the functions of cilia in embryogenesis and tissues physiology in postnatal life? 3) How does cilia dysfunction cause disease and developmental abnormalities? 4) What proteins localize in cilia, how are they targeted to this organelle, and what role do they play in cilia assembly or signaling activities?

Representative Publications:
1. Lehman JM, Laag E, Michaud EJ, Yoder BK. An essential role for dermal primary cilia in hair follicle morphogenesis.J Invest Dermatol. 2009 Feb;129(2):438-48. Epub 2008 Nov 6.

2. Kesterson RA, Berbari NF, Pasek RC, Yoder BK. Utilization of conditional alleles to study the role of the primary cilium in obesity. Methods Cell Biol. 2009;94:163-79. Epub 2009 Dec 23.

3. O'Connor AK, Kesterson RA, Yoder BK. Generating conditional mutants to analyze ciliary functions: the use of cre-lox technology to disrupt cilia in specific organs. Methods Cell Biol. 2009;93:305-30. Epub 2009 Dec 4.

4. Sharma N, Berbari NF, Yoder BK. Ciliary dysfunction in developmental abnormalities and diseases. Curr Top Dev Biol. 2008;85:371-427

5. Ohazama A, Haycraft CJ, Seppala M, Blackburn J, Ghafoor S, Cobourne M, Martinelli DC, Fan CM, Peterkova R, Lesot H, Yoder BK, Sharpe PT. Primary cilia regulate Shh activity in the control of molar tooth number. Development. 2009 Mar;136(6):897-903. Epub 2009 Feb 11.

6. Veland IR, Awan A, Pedersen LB, Yoder BK, Christensen ST. Primary cilia and signaling pathways in mammalian development, health and disease.Nephron Physiol. 2009;111(3):p39-53.

7. Berbari NF, O'Connor AK, Haycraft CJ, Yoder BK. The primary cilium as a complex signaling center.Curr Biol. 2009 Jul 14;19(13):R526-35. Review

8. Clement CA, Kristensen SG, Møllgård K, Pazour GJ, Yoder BK, Larsen LA, Christensen ST. The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation. J Cell Sci. 2009 Sep 1;122(Pt 17):3070-82. Epub 2009 Aug 4.

9. Schneider L, Cammer M, Lehman J, Nielsen SK, Guerra CF, Veland IR, Stock C, Hoffmann EK, Yoder BK, Schwab A, Satir P, Christensen ST.Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts.
Cell Physiol Biochem. 2010;25(2-3):279-92.

10. Williams CL, Masyukova SV, Yoder BK. Normal ciliogenesis requires synergy between the cystic kidney disease genes MKS-3 and NPHP-4.J Am Soc Nephrol. 2010 May;21(5):782-93. Epub 2010 Feb 11.

To find out more about Dr. Yoder's research please visit his website here