The Neurotransmitter Noradrenaline Drivesnoggin-Expressing Ectoderm Cells to ActivateN-tubulinand Become Neurons

Neurotransmitters regulate neuronal function in the nervous system and modulation of their synthesis, release, and binding by immature neurons and their targets is a major part of nervous system development. We propose that the neurotransmitter noradrenaline regulates neuronal fate during neurulation, before neurons have differentiated. The ability of noradrenaline to induce a neural fate was tested in naive ectoderm caps cut from late blastula stageXenopusembryos. Noradrenaline (10−6M) did not switch onotx-2 or NCAM and did not induce the formation of cement glands. We conclude that noradrenaline cannot induce a neural fate. By contrast, 10−8M noradrenaline activatedN-tubulinin ectoderm caps expressing the neural inducing moleculenogginby the time intact siblings had become mid-neurulae. Methoxamine, a specific α-adrenergic receptor agonist, also activatedN-tubulininnoggin-expressing caps. The α-adrenergic receptor blocker prazosin inhibited both noradrenaline- and methoxamine-induced activation ofN-tubulin. The neurotransmitters dopamine and 5-HT did not activate expression ofN-tubulin. XA-1,Otx-2,X-Delta, andXotchtranscripts were not sensitive to noradrenaline.HoxB9, which indicates posteriorization, was not activated by noradrenaline. When intact siblings were at stage 27, many cells innoggin-expressing, noradrenaline-treated caps were stained by the neuron-specific mcAb3A10. We propose that noradrenaline is an important endogenous modulator of neuronal fate, drivingnoggin-expressing cells to become neurons by binding to α-adrenergic receptors and activating a cascade that culminates in the expression of the neuronal markersN-tubulinand 3A10.