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Needing a change? Researchers find GABA is the key to metamorphosis

March 31, 2020
University of Tsukuba
Researchers have found that the neurotransmitter GABA is an essential regulator of metamorphosis in the sea squirt Ciona intestinalis. Larvae defective in GABA synthesis and transport failed to initiate metamorphosis and did not display adult organ growth. GABA positively regulated neurons expressing the reproductive maturation hormone GnRH, which is required for the key step of metamorphosis. These findings will help researchers to fully characterize the cellular changes underlying metamorphosis and explore pathway conservation among animals.

Metamorphosis, or a dramatic change in physical appearance, is a normal part of the life cycle of many animals, carried out to take advantage of different ecological niches. Yet the process of metamorphosis -- how a caterpillar becomes a butterfly, or a tadpole transforms into a frog -- is not well understood and has only been studied in a small number of species.

In a study published this week in Current Biology, a team led by researchers from the University of Tsukuba investigated the role of various neurotransmitters in the regulation of metamorphosis, identifying GABA as a key regulator in the model sea squirt Ciona intestinalis.

Ciona are some of the closest living relatives of vertebrates. Starting life as tadpole-like larvae, Ciona undergo a metamorphosis into vase-shaped adults that is triggered by their attachment to a solid surface.

"Ciona have organs called adhesive papillae that sense when the animal attaches to a surface, triggering metamorphosis," explains Professor Yasunori Sasakura, senior author. "The adhesive papillae contain sensory neurons that transmit signals to the rest of the body, suggesting that the nervous system plays an essential role in initiating metamorphosis."

To investigate the role of the nervous system in metamorphosis, the researchers treated Ciona larvae with various neurotransmitters, among which only GABA induced the physical changes associated with maturation. Upon blocking the genes required for GABA synthesis, transport, and maturation, the researchers observed decreased induction of metamorphosis, confirming they had found the right regulatory molecule.

GABA, or gamma aminobutyric acid, is one of the main neurotransmitters in mammals. It is usually thought of as an inhibitory molecule because it blocks certain signals in the brain, decreasing nervous system activity. Interestingly, however, the researchers found that this was not the case in Ciona metamorphosis.

"Using expression analysis and gene knockout/knockdown assays, we showed that GABA activates the neurons expressing gonadotropin-releasing hormone (GnRH), which is essential for reproductive maturation in vertebrates," says Professor Sasakura. "Knocking out the genes encoding GnRH showed that it is essential for metamorphosis in Ciona larvae and confirmed its place as the downstream component of GABA-mediated regulation."

Further experimentation showed that while larvae lacking GnRH could not carry out the initial steps of metamorphosis, they did exhibit normal adult organ growth. In contrast, no adult organ growth was observed in GABA mutants, suggesting that GABA is essential for all metamorphic events.

The researchers now hope to understand how the GABA-GnRH pathway causes the dramatic physical changes that occur during Ciona metamorphosis and, given the wide conservation of these molecules among animals, to explore whether the GABA-GnRH mechanism plays a role in the metamorphosis of other animal species.

Story Source:

Materials provided by University of Tsukuba. Note: Content may be edited for style and length.

Journal Reference:

  1. Akiko Hozumi, Shohei Matsunobu, Kaoru Mita, Nicholas Treen, Takaho Sugihara, Takeo Horie, Tetsushi Sakuma, Takashi Yamamoto, Akira Shiraishi, Mayuko Hamada, Noriyuki Satoh, Keisuke Sakurai, Honoo Satake, Yasunori Sasakura. GABA-Induced GnRH Release Triggers Chordate Metamorphosis. Current Biology, 2020; DOI: 10.1016/j.cub.2020.02.003

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University of Tsukuba. "Needing a change? Researchers find GABA is the key to metamorphosis." ScienceDaily. ScienceDaily, 31 March 2020. <>.
University of Tsukuba. (2020, March 31). Needing a change? Researchers find GABA is the key to metamorphosis. ScienceDaily. Retrieved May 20, 2024 from
University of Tsukuba. "Needing a change? Researchers find GABA is the key to metamorphosis." ScienceDaily. (accessed May 20, 2024).

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