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We are interested in how circuitry that drives locomotory behavior is
constructed during development. During embryogenesis, many cells navigate
extensively to their final destinations, where they form precise connections
with their neighbors. We intend to define the molecules and mechanisms that
guide two cell types (motor neurons and neural crest) to their targets, using
chick and zebrafish as model systems. Motor neurons originate in the ventral neural tube and extend their axons to innervate particular muscles in the limb. Our previous studies showed that these cells and their migratory pathways expressed unique combinations of Eph receptor tyrosine kinases (RTKs) and their ligands, the ephrins. We also showed that distinct subsets of motor neurons that express EphA4 RTK respond differently to ephrin-A5. Recently, we demonstrated that chick ephexin, a downstream intracellular signaling molecule that is phosphorylated by EphA4, is required for axon stalling at the base of the limb. Our current research focuses on unraveling the mechanisms that account for precise axon pathfinding to the limb. Neural crest cells, a stem cell-like population, emanate from the dorsal neural tube and migrate along stereotypical pathways to their target regions to form various derivatives including sensory/sympathetic ganglia, components of the heart and craniofacial skeleton, and pigment cells. We are interested in how this stem cell-like population generates such a diverse array of derivatives. Furthermore, we are analyzing how various molecules contribute to neural crest motility, directed movement, and settling patterns. Together, these studies will yield important insights about the positive and negative cues that sculpt precise patterns of cellular architecture during development.
- Sahin M, Greer PL, Lin MZ, Poucher H, Eberhart J, Schmidt S, Wright TM, Shamah SM, O’Connell S, Cowan CW, Hu L, Goldberg JL, Debant A, Corfas G, Krull CE, Greenberg ME (2005) Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone collapse. Neuron 46, 191-204.
- Krull CE (2005) Comm-ing across the midline. Nature Neuroscience 8, 131-132.
- Cramer KS, Bermingham-McDonough O, Krull CE, Rubel EW (2004) EphA4 signaling promotes axon segregation in the developing auditory system. Dev. Biology 269, 26-35.
- Eberhart J, Barr J, O'Connell S, Flagg A , Swartz ME, Cramer K, Tosney, KW, Pasquale EB, Krull CE (2004) Ephrin-A5 exerts positive or inhibitory effects on distinct subsets of EphA4-positive neurons. J. Neurosci. 24, 1070-1078.
- Krull CE (2004) A primer on using in ovo electroporation to analyze gene function. Dev. Dyn. 229, 433-439.
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