For the nervous system to function properly, it is crucial that embryonic neurons acquire appropriate identities so they can develop the properties necessary for their later functions. The longterm goal of our laboratory is to understand the mechanisms underlying these processes. These mechanisms will be investigated by studying development of individually identified primary motoneurons in embryonic zebrafish. Our hypothesis is that the identities of primary motoneurons are specified by a series of signals that regulate expression of transcription factors that control neuronal identity and later features of development, such as axonal pathfinding. A series of experiments to test aspects of this hypothesis are proposed. Zebrafish primary motoneurons initially express a specific transcription factor, islet1, which is then downregulated; later islet1 or a related gene, islet2 is expressed in each specific primary motoneuron. The roles of the distinct phases of islet gene expression in motoneuron identity and axonal pathfinding will be tested using mutants and morpholino antisense oligonucleotides to knock down gene function. Retinoic acid, a well-known teratogen that can have devastating effects on human embryos, is synthesized in zebrafish during the time that primary motoneurons are being specified. Exposure to exogenous retinoic acid alters motoneuron numbers and patterning. The role of endogenous retinoic acid in motoneuron specification, and its interactions with other signals including the Hedgehog and Delta/Notch pathways, will be tested by a series of genetic gain- and loss-of-function experiments. The effects of retinoic acid on regulation of somite-derived signals that affect motoneuron identity will also be examined; potential signals will be identified using differential molecular screens. Interactions between specific primary motoneurons and the muscle fibers they innervate regulate their identities and survival. The role of the Delta/Notch signaling pathway in this process will be tested using a genetic approach. Although many genes regulating motoneuron development are known, many remain undiscovered. A mutagenesis screen will be undertaken to identify new genes involved in specifying motoneuron identities.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
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Gwinn, Katrina
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University of Oregon
Other Basic Sciences
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United States
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Van Ryswyk, Liesl; Simonson, Levi; Eisen, Judith S (2014) The role of inab in axon morphology of an identified zebrafish motoneuron. PLoS One 9:e88631
Seredick, Steve; Hutchinson, Sarah A; Van Ryswyk, Liesl et al. (2014) Lhx3 and Lhx4 suppress Kolmer-Agduhr interneuron characteristics within zebrafish axial motoneurons. Development 141:3900-9
Seredick, Steve D; Van Ryswyk, Liesl; Hutchinson, Sarah A et al. (2012) Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics. Neural Dev 7:35
Tallafuss, Alexandra; Gibson, Dan; Morcos, Paul et al. (2012) Turning gene function ON and OFF using sense and antisense photo-morpholinos in zebrafish. Development 139:1691-9
Honjo, Yasuko; Payne, Laurel; Eisen, Judith S (2011) Somatosensory mechanisms in zebrafish lacking dorsal root ganglia. J Anat 218:271-6
Hale, Laura A; Fowler, Daniel K; Eisen, Judith S (2011) Netrin signaling breaks the equivalence between two identified zebrafish motoneurons revealing a new role of intermediate targets. PLoS One 6:e25841
Krull, Catherine E; Eisen, Judith S (2010) Mechanisms of growth cone repulsion. F1000 Biol Rep 2:6
Tallafuss, Alexandra; Trepman, Alissa; Eisen, Judith S (2009) DeltaA mRNA and protein distribution in the zebrafish nervous system. Dev Dyn 238:3226-36
Eisen, Judith S; Smith, James C (2008) Controlling morpholino experiments: don't stop making antisense. Development 135:1735-43
Honjo, Yasuko; Kniss, Jonathan; Eisen, Judith S (2008) Neuregulin-mediated ErbB3 signaling is required for formation of zebrafish dorsal root ganglion neurons. Development 135:2615-25

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