PgmNr Z566: Longterm Regulation of Zebrafish Behavior by Maternal Rest/NRSF is Mediated by snap25a/b.

Authors:
Howard I. Sirotkin 1 ; Cara E. Moravec 1 ; John Samuel 2 ; Wei Weng 3 ; Ian C. Wood 4


Institutes
1) Stony Brook University, Stony Brook, NY; 2) Seneca College, Toronto, Canada; 3) Ingenious Targeting Labs, Ronkonkoma, NY; 4) University of Leeds, Leeds, UK.


Abstract:

During embryonic development, regulation of gene expression is key to creating the many subtypes of cells that an organism needs thoughout out its lifetime. Recent work has shown that maternal genetics and environmental factors have lifelong consequences on diverse processes ranging from immune function to stress responses. The RE1-silencing transcription factor (Rest) is a transcriptional repressor that interacts with chromatin-modifying complexes to repress transcription of neural specific genes during early development. In zebrafish, rest is maternally expressed and the chromatin modifications mediated by Rest have may exert long-term effects. We found that maternally supplied rest regulates expression of target genes during larval development and has lifelong impacts on behavior.  Larvae deprived of maternal rest are hyperactive and show atypical spatial preferences. As adults, male but not female fish deprived of maternal rest present with atypical spatial preferences in a novel environment assay. To identify key targets of maternally supplied rest, we utilized transcriptome sequencing and found 158 genes that are repressed by maternal rest in blastula stages embryos. Expression analysis revealed that maternal rest is required to repress expression of several of these targets for extended periods (up to 6 dpf). Disruption of the RE1 sites in either of two of these genes, snap25a and snap25b resulted in behaviors that recapitulate the hyperactivity phenotype caused by absence of maternal rest.  Both the maternal rest mutants and snap25a RE1 site mutants have changes to the primary motor neuron architecture that is characteristic of overexpression of snap25. These results demonstrate that maternal rest represses snap25a/b to modulate larval behavior and that early Rest activity has lifelong behavioral impacts.



ZFIN Genetics Index
1. rest
2. snap25a
3. snap25b