defects in ribbon-associated proteins are specific to mutants involving proteins that are critical for photoreceptor synapse formation.

Concomitant with a presynaptic malformation and prior to retinal degeneration, we show that mice lacking Tulp1 have a reduced dendritic composition. Due to the photoreceptor presynaptic structural defects in the tulp1–/– retina, we hypothesize that there should be a reduction in the signaling to second-order neurons. The attenuation of photoreceptor signaling has been associated with the consequent alterations in the downstream neural layers of the retina (Marc et al. 2003; Léveillard et al. 2004). Therefore, we hypothesize that the reduction of the DBC dendritic composition in tulp1–/– mice is a direct result of a decrease in neurotrophic and/or neurotransmitter release. It is important to note that in the rd10 retina, a reduction in length and branching of DBC dendrites is noted only during the height of photoreceptor cell death. The atrophy of postsynaptic dendritic processes has been observed in many models of retinal degeneration, and has been termed retraction to denote the negative remodeling from a prior developed state as a direct and downstream effect of photoreceptor cell death (Marc et al. 2003; Gargini et al. 2007). However, in the tulp1–/– retina, shortened dendrite lengths as well as reduced branching are detected prior to photoreceptor cell death.

In conclusion, the absence of Tulp1 results in abnormalities that affect structure and function in multiple retinal sites. The photoreceptor degeneration and OS defects of tulp1–/– mice have been described, providing evidence that Tulp1 may function in the polarized transport of proteins at the apical end of the photoreceptor (Hagstrom et al. 1999; 2001). We have shown that Tulp1 interacts with Actin and Dynamin-1, two proteins known to be critical in the cytoskeletal scaffold and involved in the molecular pathway of vesicular protein transport occurring from the IS to the OS and in vesicle cycling at photoreceptor terminals (Xi et al. 2005; 2007). Thus, Tulp1 may be functioning in intracellular protein trafficking throughout the photoreceptor cell, and in its absence, two distinct abnormalities at polar ends of the cell are highlighted. Here we provide evidence that photoreceptor ribbon synapses and DBC dendrites are also severely affected at an early age. These new findings indicate that Tulp1 is essential for photoreceptor cell survival, and is also required for the proper development of the photoreceptor synapse.

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Chapter 12

Growth-Associated Protein43 (GAP43)

Is a Biochemical Marker for the Whole Period of Fish Optic Nerve Regeneration

Manabu Kaneda, Mikiko Nagashima, Kazuhiro Mawatari, Tomoya Nunome, Kenichiro Muramoto, Kayo Sugitani, and Satoru Kato

Abstract In adult visual system, goldfish can regrow their axons and fully restore their visual function even after optic nerve transection. The optic nerve regeneration process in goldfish is very long and it takes about a half year to fully recover visual function via synaptic refinement. Therefore, we investigated time course of growth-associated protein 43 (GAP43) expression in the goldfish retina for over 6 months after axotomy. In the control retina, very weak immunoreactivity could be seen in the retinal ganglion cells (RGCs). The immunoreactivity of GAP43 started to increase in the RGCs at 5 days, peaked at 7–20 days and then gradually decreased at 30–40 days after axotomy. The weak but significant immunoreactivity of GAP43 in the RGCs continued during 50–90 days and slowly returned to the control level by 180 days after lesion. The levels of GAP43 mRNA showed a biphasic pattern; a short-peak increase (9-folds) at 1–3 weeks and a long plateau increase (5-folds) at 50–120 days after axotomy. Thereafter, the levels declined to the control value by 180 days after axotomy. The changes of chasing behavior of pair of goldfish with bilaterally axotomized optic nerve also showed a slow biphasic recovery pattern in time course. Although further experiment is needed to elucidate the role of GAP43 in the regrowing axon terminals, the GAP43 is a good biochemical marker for monitoring the whole period of optic nerve regeneration in fish.

12.1 Introduction

Unlike mammals, fish optic nerve regenerates and restores the visual function after optic nerve lesion (Sperry 1948). The optic nerve regeneration process in fish is a long-lasting one. We classified four periods of goldfish optic nerve regeneration after nerve lesion from morphological, biochemical and behavioral results (Kato et al. 1999, 2007). The first period is a preparation period within 5–6 days after nerve

S. Kato (B)

Department of Molecular Neurobiology, University of Kanazawa, Kanazawa 920-8640, Japan e-mail: satoru@med.kanazawa-u.ac.jp

Medicine and Biology 664, DOI 10.1007/978-1-4419-1399-9_12,C Springer Science+Business Media, LLC 2010