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Mol Brain. 2016 Jan 8;9:6. doi: 10.1186/s13041-016-0187-5.

Diversification of behavior and postsynaptic properties by netrin-G presynaptic adhesion family proteins.

Author information

1
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. zhangqi@brain.riken.jp.
2
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. gotohiromichi@brain.riken.jp.
3
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. sachiko.akiyoshi@gen.mpg.de.
4
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. prosselkov@brain.riken.jp.
5
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. sano@brain.riken.jp.
6
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. mtkwh40bg@brain.riken.jp.
7
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. yaguchi0401@gmail.com.
8
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. nakashib@brain.riken.jp.
9
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. sitohara@brain.riken.jp.

Abstract

BACKGROUND:

Vertebrate-specific neuronal genes are expected to play a critical role in the diversification and evolution of higher brain functions. Among them, the glycosylphosphatidylinositol (GPI)-anchored netrin-G subfamily members in the UNC6/netrin family are unique in their differential expression patterns in many neuronal circuits, and differential binding ability to their cognate homologous post-synaptic receptors.

RESULTS:

To gain insight into the roles of these genes in higher brain functions, we performed comprehensive behavioral batteries using netrin-G knockout mice. We found that two netrin-G paralogs that recently diverged in evolution, netrin-G1 and netrin-G2 (gene symbols: Ntng1 and Ntng2, respectively), were responsible for complementary behavioral functions. Netrin-G2, but not netrin-G1, encoded demanding sensorimotor functions. Both paralogs were responsible for complex vertebrate-specific cognitive functions and fine-scale regulation of basic adaptive behaviors conserved between invertebrates and vertebrates, such as spatial reference and working memory, attention, impulsivity and anxiety etc. Remarkably, netrin-G1 and netrin-G2 encoded a genetic "division of labor" in behavioral regulation, selectively mediating different tasks or even different details of the same task. At the cellular level, netrin-G1 and netrin-G2 differentially regulated the sub-synaptic localization of their cognate receptors and differentiated the properties of postsynaptic scaffold proteins in complementary neural pathways.

CONCLUSIONS:

Pre-synaptic netrin-G1 and netrin-G2 diversify the complexity of vertebrate behaviors and differentially regulate post-synaptic properties. Our findings constitute the first genetic analysis of the behavioral and synaptic diversification roles of a vertebrate GPI protein and presynaptic adhesion molecule family.

PMID:
26746425
PMCID:
PMC4706652
DOI:
10.1186/s13041-016-0187-5
[Indexed for MEDLINE]
Free PMC Article

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