The Knapik laboratory is interested in the molecular and cellular mechanisms that govern stem cell specification.   The Knapik laboratory's overall goal is to understand how specific gene function guides a cell from a pluripotent precursor to a terminally differentiated, highly specialized cell and how basic cellular functions, such as protein transport and modification, control the maturation of developing tissues and organs.

Lab members have found that the tfap2a and foxd3 genes are critical for Neural Crest (NC) specification.   Loss-of-function mutants revealed that tfap2a is acting at the transition step from NC stem cells to lineage specific cell fates. In its absence, cranial neural crest progenitors fail to differentiate and die by apoptosis. In contrast, the NC stem cells that are foxd3 deficient appear to be affected at earlier stages of development.  The Knapik lab has discovered that the two genes control parallel but interacting pathways and that a combined loss of function of tfap2a and foxd3 leads to an almost complete elimination of all NCC derivatives.

In collaboration with the Bruce Appel laboratory, the Knapik lab is analyzing the neural crest stem cell population to determine which steps in their development depend on the combined action of the two pathways. The final differentiation of the NC derived craniofacial cartilage relies on a robust cellular secretory pathway and an elaborate post-translational modification of cartilage extracellular matrix (ECM) proteins. To better understand these critical processes, the Knapik lab is analyzing loss-of-function mutations affecting key components of the secretory pathway and ER/Golgi N-glycosylation during development. In collaboration with the Liliana Solnica-Krezel laboratory, lab members have found that the bulldog mutation blocks cellular transport of ECM proteins, a defect that severely perturbs cartilage development and maturation.

For more information about Dr. Knapik visit her Vanderbilt Faculty Page

RECENT PUBLICATIONS

A major zebrafish polymorphism resource for genetic mapping.  Genome Biology (2007) 8: R55