Our long-term goal is to understand how neurons acquire their individual identities and how they express those identities by developing the appropriate set of differentiated characteristics, including cell shape and axonal projection. Appropriate expression of these characteristics is important for proper nervous system function. We plan to study these issues in embryonic zebrafish where we can examine the development of individually identified motoneurons in living embryos. We hypothesize that individual neurons have intrinsic differences that arise, at least in part, because of environmental interactions such as: i) inductions that determine which cells adopt a motoneuronal fate, ii) position-dependent signals that determine axonal trajectories and thus synaptic targets of individual motoneurons and iii) competitive interactions that determine the fates of motoneurons that form an equivalence pair. We propose to examine the nature of morphological differences between individually identified motoneurons. By culturing these neurons singly, we will learn whether these differences are intrinsic to the cells, or require extrinsic environmental signals. By culturing neurons at different times, we will also learn when these differences arise. We propose to examine whether inductive signaling from segmented mesoderm patterns motoneurons in the spinal cord. We will test this idea by creating genetic mosaics by transplanting precursors of segmented mesoderm between wild types and mutants which lack segmented mesoderm and motoneurons. We propose to learn about the genetic control of motoneuronal phenotype. We will produce and isolate mutants in which motoneuronal development is altered. We will characterize these mutants to learn about the specific defects. We will be particularly interested in mutants in which position- dependent signals are affected. We propose to learn about competitive interactions between specific motoneurons that form an equivalence pair. We will transplant individual motoneurons to new locations to examine the interactions between them. We will learn whether death of a specific motoneuron can be prevented, and we will learn its fate when it survives. We will learn whether motoneurons that do not typically behave as an equivalence pair can be induced to do so.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurology B Subcommittee 2 (NEUB)
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University of Oregon
Other Domestic Higher Education
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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