Zebrafish rgs4 is essential for motility and axonogenesis mediated by Akt signaling.
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.
Graduate Institute of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, 33383, Taiwan. yccheng@mail.cgu.edu.tw
Yi-Chuan
YC
Cheng
Paul J
PJ
Scotting
Li-Sung
LS
Hsu
Sheng-Jia
SJ
Lin
Hung-Yu
HY
Shih
Fu-Yu
FY
Hsieh
Hui-Lan
HL
Wu
Chu-Li
CL
Tsao
Chia-Jung
CJ
Shen
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D010802:Phylogeny; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020710:RGS Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*
D020710:RGS Proteins; C098799:RGS4 protein; D051057:Proto-Oncogene Proteins c-akt