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[P244]: Isolation and characterization of a candidate component of UNC‐6/netrin signaling in axon guidance and distal tip cell migration in C. elegans
Author(s) -
Plummer J.T.,
Brown L.,
Culotti J.G
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.303
Subject(s) - netrin , axon guidance , microbiology and biotechnology , biology , component (thermodynamics) , neuroscience , axon , physics , thermodynamics
Commissure formation requires adaptive responses of axonal growth cones to midline cues. We describe the zebrafish habenular commissure, the sole axonal crossing point in the dorsal forebrain of teleosts, as a model for studying commissure development. We have used lipophilic dyes and electroporationmediated transfection as in vivo labelling techniques to document habenular commissure formation. These analyses have revealed novel growth cone dynamics at the midline. In embryos with mutations in esrom, commissural axons navigate to the roof plate of the diencephalon, but stall and ultimately fail to cross. While stalled, growth cones are dynamic and exhibit extensive protrusive activity. esrom encodes the zebrafish ortholog of PAM/PHR/Highwire/RPM-1, an immense molecule with E3 ubiquitin ligase activity that interacts with multiple signal transduction pathways. We are using genetics, immunohistochemistry, receptor affinity probe assays, transient unilateral transfection of the brain, and live imaging to elucidate the axon guidance signals and growth cone responses required for proper habenular commissure formation, and to understand how this process is disrupted in esrom. Axon segments within the commissure, but not elsewhere, have EphB receptors localized to the plasma membrane. Esrom is also required for proper retinal axon sorting and topographic mapping, a process dependent on Eph–Ephrin signaling. We are exploring the hypothesis that Esrom acts in a pathway to regulate Eph signaling in the growth cone during habenular commissure formation. Midline axon guidance and Eph signaling offer a new context for understanding the cellular functions of Esrom, an enigmatic and complex molecule. EphBs are required for proper corpus callosum and habenular commissure formation in mammals. We speculate that mechanisms of habenular commissure formation in teleosts may share common mechanisms with dorsal forebrain decussation in higher vertebrates.