Research Abstract:
The Hodzic lab focuses on the role of LINC complexes (Linkers of the Nucleoskeleton to the Cytoskeleton) in nucleokinesis and its relevance to nuclear migration in neuronal and muscle cells. Conditional mouse transgenic approaches are used to target the retina, cortex and skeletal muscle. The specific targeting of cortex and retina is motivated by the fact that 1) they display extensive interkinetic nuclear migration during post-mitotic cell specification, 2) they rely on glial-guided neuronal migration for their laminated pattern, 3) they are organized in laminar nuclear layers whose disorganization can be tested in vivo and 4) they allow the purification of different neuronal cell types amenable to study nuclear dynamics in vitro. The retina further allows the use of non-invasive methods to directly assess disruptive phenotypes. These experiments could significantly enhance our understanding of retina and cortex development and homeostasis and to uncover new molecular etiologies associated human diseases resulting from neuronal migration defects. Targeting of skeletal muscles will further examine the role of LINC complexes in the anchorage of synaptic nuclei beneath the post-synaptic apparatus.
Selected Publications:
Stewart-Hutchinson PJ, Hale CM, Wirtz D, Hodzic D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp. Cell Res. 2008 314(8): 1892-1905.
Ketema M, Wilhelmsen K, Kuikman I, Janssen H, Hodzic D, Sonnenberg A. Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin. J Cell Sci. 2007 120(Pt 19): 3384-3394.
Liu Q, Pante N, Misteli T, Elsagga M, Crisp M, Hodzic D, Burke B, Roux J. Functional association of Sun1 with nuclear pore complexes. J Cell Biol 2007 178: 785-798.
Schmitt J, Benavente R, Hodzic D, Hoog C, Stewart CL, Alsheimer M. Transmembrane protein Sun2 is involved in tethering mammalian meiotic telomeres to the nuclear envelope. Proc Natl Acad Sci USA 2007 104: 7426-7431.
Crisp M, Liu Q, Roux K, Rattner JB, Shanahan C, Burke B, Stahl PD, Hodzic D. Coupling of the nucleus and cytoplasm: role of the LINC complex. J. Cell Biol. 2006 172: 41-53.
Last Updated: 11/18/2009 |