Discovered: the neuroendocrine circuit that dictates when fish are ready to hatch

Researchers have uncovered a previously unknown yet crucial role for thyrotropin-releasing hormone (Trh) in zebrafish hatching and reveal how this hormone activates a transient neuroendocrine circuit that controls when fish larvae are ready to leave the egg and swim free. For egg-born animals, hatching marks a pivotal shift, transitioning from the sheltered environment of an egg capsule to external conditions. This crucial event is not strictly hardwired into the embryo’s developmental program. Rather, hatching is a regulated process influenced by both developmental milestones and external cues, including sensory inputs like mechanical or acoustic signals, which optimize the embryo's chances of survival. In fish, hatching strategies can vary widely, with some species delaying the event for months until favorable conditions arise. Others time it to specific periods such as day or night. Fish embryos achieve hatching by secreting enzymes from specialized hatching gland cells to break down the chorion (the protective envelope that surrounds the developing embryo). While the physiology of this gland is well understood, the neural mechanisms driving enzyme secretion to trigger hatching remain unclear. Using CRISPR-Cas9-mediated inactivation of the trh gene in zebrafish, Deodatta Gajbhiye and colleagues discovered that fish with mutations of this gene were unable to hatch. By mapping the projections of Trh-producing neurons in the hypothalamus of zebrafish embryos, Gajbhiye et al. found that this hormone directly stimulates the hatching gland to release enzymes that degrade the chorion, initiating hatching. What’s more, the strong presence of Trh in these neural projections before hatching disappears afterward, highlighting the transient, hatching-specific nature of the neuroendocrine circuit. “How the transient Trh circuit is precisely activated for hatching to occur at the perfect time and scenario is not yet known,” write Francesco Argenton and Yoav Gothilf in a related Perspective.