Int. J. Dev. Biol. 63: 37 - 43 (2019)
doi: 10.1387/ijdb.180384hk
© UPV/EHU Press

Axis elongation during Xenopus tail-bud stage is regulated by GABA expressed in the anterior-to-mid neural tube

Tomoyo Furukawa1, Yuki Yamasaki2, Yusuke Hara2,3, Chisa Otsuki4, Hiroko Maki5, Tomoyoshi Soga5, Yuki Moriyama6 and Hiroki Kuroda*,1,2,3,4,5

1Graduate School of Science and Technology, Shizuoka University, Shizuoka, 2Graduate School of Media and Governance, Keio University, Kanagawa, 3AOI laboratory, Keio Research Institute at SFC, Shizuoka, 4Faculty of Environment and Information Studies, Keio University, Kanagawa, 5Institute for Advanced Biosciences, Keio University, Yamagata and 6Faculty of Science and Engineering, Chuo University, Tokyo, Japan

ABSTRACT The receptors of gamma-aminobutyric acid (GABA), which is a well-known neurotransmitter, are expressed in the anterior-to-mid neural tube at an early stage of Xenopus development, but there has been no report on the role of GABA in the presumptive central nervous system. Therefore, we tried to reveal the function of GABA for Xenopus early embryogenesis. We first confirmed that the region expressing a gene encoding glutamate decarboxylase 1 (gad1), which is an enzyme that catalyzes the decarboxylation of L-glutamate to GABA, overlapped with that of several genes encoding GABA receptors (gabr) in the neural tube. Metabolome analysis of culture medium of dorsal tail-bud explants containing the neural tube region of tail-bud stage embryos also revealed that GABA was expressed at this stage. Then, we examined the treatment of pentylenetetrazole (PTZ) and picrotoxin (PTX), which are known as inhibitors of GABA receptors (GABA-R), on the early stages of Xenopus embryogenesis, and found that axis elongation in the tail-bud was inhibited by both treatments, and these phenotypic effects were rescued by co-treatment with GABA. Moreover, our spatial- and temporal-specific inhibitor treatments revealed that the gabr- and gad1-overlapped region, which presents at the anterior-to-mid neural tube during the tail-bud stages, was much more sensitive to PTZ and thus caused severe inhibition of axis elongation. Taken together, our results indicate that the small ligand molecule GABA functions as a regulator to induce the axis elongation event in the tail-bud during early embryogenesis via direct stimulation of the neural tube and indirect stimulation of the surrounding area.

Keywords:

GABA, Xenopus, neural tube, convergent extension, pentylenetetrazole

*Corresponding author e-mail: hkuroda@sfc.keio.ac.jp