The neurotransmitter noradrenaline drives noggin-expressing ectoderm cells to activate N-tubulin and become neurons

Abstract

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 stage Xenopus embryos. Noradrenaline (10(-6) M) did not switch on otx-2 or NCAM and did not induce the formation of cement glands. We conclude that noradrenaline cannot induce a neural fate. By contrast, 10(-8) M noradrenaline activated N-tubulin in ectoderm caps expressing the neural inducing molecule noggin by the time intact siblings had become mid-neurulae. Methoxamine, a specific alpha-adrenergic receptor agonist, also activated N-tubulin in noggin-expressing caps. The alpha-adrenergic receptor blocker prazosin inhibited both noradrenaline- and methoxamine-induced activation of N-tubulin. The neurotransmitters dopamine and 5-HT did not activate expression of N-tubulin. XA-1, Otx-2, X-Delta, and Xotch transcripts were not sensitive to noradrenaline. HoxB9, which indicates posteriorization, was not activated by noradrenaline. When intact siblings were at stage 27, many cells in noggin-expressing, noradrenaline-treated caps were stained by the neuron-specific mcAb3A10. We propose that noradrenaline is an important endogenous modulator of neuronal fate, driving noggin-expressing cells to become neurons by binding to alpha-adrenergic receptors and activating a cascade that culminates in the expression of the neuronal markers N-tubulin and 3A10.