Zebrafish rgs4 is essential for motility and axonogenesis mediated by Akt signaling

Yi Chuan Cheng*, Paul J. Scotting, Li Sung Hsu, Sheng Jia Lin, Hung Yu Shih, Fu Yu Hsieh, Hui Lan Wu, Chu Li Tsao, Chia Jung Shen

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

30 Scopus citations

Abstract

The schizophrenia susceptibility gene, Rgs4, is one of the most intensively studied regulators of G-protein signaling members, well known to be fundamental in regulating neurotransmission. However, little is known about its role in the developing nervous system. We have isolated zebrafish rgs4 and shown that it is transcribed in the developing nervous system. Rgs4 knockdown did not affect neuron number and patterning but resulted in locomotion defects and aberrant development of axons. This was confirmed using a selective Rgs4 inhibitor, CCG-4986. Rgs4 knockdown also attenuated the level of phosphorylated-Akt1, and injection of constitutively-activated AKT1 rescued the motility defects and axonal phenotypes in the spinal cord but not in the hindbrain and trigeminal neurons. Our in vivo analysis reveals a novel role for Rgs4 in regulating axonogenesis during embryogenesis, which is mediated by another schizophrenia-associated gene, Akt1, in a region-specific manner.

Original languageEnglish
Pages (from-to)935-950
Number of pages16
JournalCellular and Molecular Life Sciences
Volume70
Issue number5
DOIs
StatePublished - 03 2013

Keywords

  • Akt
  • Axonogenesis
  • Rgs4
  • Zebrafish

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