The objective of this proposal is to study the embryogenesis of the vertebrate extraocular sensory-motor system. The research will address problems of when and how eye muscles, motoneurons and vestibular neurons become spatially programmed and functionally specified to produce eye movements. The extraocular system is an excellent model to assess causality in development because of its compartmental organization and accessibility to both experimental manipulation and assay using combined morphological and electrophysiological methods. Most research will be conducted in avian embryos because of their suitability for descriptive and analytical experiments; however, to distinguish elements of a common phylogenetic blueprint from species-specific derived characteristics, studies of neurogenesis and extraocular myogenesis in other vertebrate embryos are proposed.
Three specific aims are outlined to reveal the ontogenetic history of networks linking vestibular neurons, extraocular motoneurons and eye muscles that produce movement about defined axes of rotation. First, the origins and migrations of eye muscle precursors, both myogenic and neural crest-derived, will be studied using a variety of fluorescent and retroviral markers. When and where eye motoneurons and axons arise in the neuroepithelium and subsequently make contact with peripheral tissues will be documented.
The second aim will define the location, axonal trajectory and arborization pattern of vestibulo-ocular neurons with particular focus on those correlated with horizontal eye rotation. The embryonic lineage of each vestibular subnucleus will be defined. Intra- and extracellular analyses of neuronal organization will utilize biocytin and fluorescent probes complemented by single cell intracellular electrophysiology. Third, we will define when and where spatial properties of each extraocular component are acquired and examine hypothesized specific interactions that promote positional specification of all components. This will be done by surgically deleting or altering the spatial relations among rhombomeres, muscle precursors, the neural crest and the optic vesicle. This work uses avian chimeras, discrete intracellular markers, fluorescent and other molecular probes. These experiments will define the processes that coordinate assembly of the eye movement sensory-motor network and provide new insights into the general problem of neuronal and muscle specification.
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