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Homotypic Fusion and Protein Sorting (HOPS) and Class C-core Vacuole/Endosome Tethering (CORVET) complexes regulate the correct fusion of endolysosomal bodies. Mutations in core proteins (VPS11, VPS16, VPS18, and VPS33) have been linked with multiple neurological disorders, including mucopolysaccharidosis (MPS), genetic leukoencephalopathy (gLE), and dystonia. Mutations in human Vacuolar Protein Sorting 16 (VPS16) have been associated with MPS and dystonia. In this study, we generated and characterized a zebrafish vps16(-/-) mutant line using immunohistochemical and behavioral approaches. The loss of Vps16 function caused multiple systemic defects, hypomyelination, and increased neuronal cell death. Behavioral analysis showed a progressive loss of visuomotor response and reduced motor response and habituation to acoustic/tap stimuli in mutants. Finally, using a novel multiple-round acoustic/tap stimuli test, mutants showed intermediate memory deficits. Together, these data demonstrate that zebrafish vps16(-/-) mutants show systemic defects, neurological and motor system pathologies, and cognitive impairment. This is the first study to report behavior abnormalities and memory deficiencies in a zebrafish vps16(-/-) mutant line. Finally, we conclude that the deficits observed in vps16(-/-) zebrafish mutants do not mimic pathologies associated with dystonia, but more align to abnormalities associated with MPS and gLE. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.02.051 Byline: Angela D. Hoptak-Solga (a), Sarah Nielsen (a), Isha Jain (a), Ryan Thummel (b), David R. Hyde (b), M. Kathryn Iovine (a) Keywords: Bone growth; short fin; Regeneration; Zebrafish; Cell proliferation; Cx43; GJIC Abstract: In zebrafish, mutations in the gap junction gene connexin43 lead to short bony fin ray segments that give rise to the short fin phenotype. The sof.sup.b123 mutant exhibits fins that are half the length of wild-type fins and have reduced levels of cx43 mRNA. We find that sof.sup.b123 regenerating fins exhibit reduced levels of cell proliferation. Interestingly, the number of dividing cells per unit length of fin growth is similar between wild-type and mutant fins, suggesting that the number of cells that enter the cell cycle is specifically affected in sof.sup.b123 . Expression of cx43 is identified in mitotic cells, which further suggests that Cx43 may contribute to establishing or maintaining the population of dividing cells. Indeed, missense alleles exhibiting high or low levels of gap junctional communication reveal a correlation between defects in direct cell-cell communication, cell proliferation, and segment length. Finally, targeted gene knockdown of cx43 in adult regenerating fins recapitulates the sof.sup.b123 phenotype, revealing that the loss of Cx43 is sufficient to reduce both cell proliferation and segment length. We hypothesize that the level of gap junctional intercellular communication among dividing cells regulates the level of cell proliferation and ultimately regulates bone growth. Author Affiliation: (a) Lehigh University, Department of Biological Sciences, 111 Research Drive, Iacocca B-217, Bethlehem, PA 18015, USA (b) University of Notre Dame, Department of Biological Sciences and Center for Zebrafish Research, Notre Dame, IN 46556, USA Article History: Received 10 October 2007; Revised 4 February 2008; Accepted 28 February 2008

Vertebrate Hox genes are generally believed to initiate expression at the primitive streak or early neural plate stages. The timing and spatial restrictions of the Hox expression patterns during these stages correlate well with their demonstrated role in axial patterning. Here we demonstrate that one zebrafish hoxc13 ortholog, hoxc13a, has an expression pattern in the developing tail bud that is consistent with the gene playing a role in axial patterning. However, the second hoxc13 ortholog, hoxc13b, is maternally expressed and is detectable in every cell of early cleavage embryos through gastrulae. In addition, both transcript and protein are detectable at these stages. At 19 h post fertilization (hpf), hoxc13b expression is up-regulated in the tail bud, becoming restricted to the tail bud by 24 hpf. Importantly, by 24 hpf, hoxc13b morphants show a specific developmental delay, which can be rescued by co-injecting synthetic capped hoxc13a or hoxc13b message. These data suggest some functional divergence due to altered expression patterns of the two hoxc13 orthologs after duplication. Further characterization of the hoxc13b morphant delay reveals that it is biphasic in nature, with the first phase of the delay occurring before gastrulation, suggesting a new role for vertebrate Hox genes before their conserved role in axial patterning. The extent of the delay does not change through 20 hpf; however, an additional delay emerges at this time. Notably, this second phase of the delay correlates with hoxc13b expression pattern becoming restricted to the tail bud. Keywords: Blastula; Embryogenesis; Gastrulation; Hox genes; Hoxe13a; Hoxc13b; Maternal transcript; Spatial colinearity; Subfunctionalization; Zebrafish

The impact of dynamic regulation of different microRNAs (miRNAs) on the regeneration of the fin of a zebrafish is studied. The depletion of the mIR-133 by the Fibroblast growth factor (Fgf) receptor is shown to highly promote the appendage regeneration in the studied fish.