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Calcineurin Primes Immature Gonadotropin-Releasing Hormone-Secreting Neuroendocrine Cells for Migration

Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche and Drug and Food Biotechnology Center (R.Z., S.T., J.E., C.D., F.C., P.L.C., A.A.G.), Università degli Studi del Piemonte Orientale "A. Avogadro," 28100 Novara, Italy; and Department of Endocrinology (R.M., A.C.), Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy

Address all correspondence and requests for reprints to: Armando A. Genazzani, DiSCAFF, Università del Piemonte Orientale, Via Bovio 6, 28100 Novara, Italy. E-mail: Genazzani{at}pharm.unipmn.it.

During development, many neurons display calcium-dependent migration, but the role of this messenger in regulating gene expression leading to this event has not yet been elucidated. Among the decoders of calcium signals is calcineurin, a Ca²⁺/calmodulin serine/threonine phosphatase that has been involved in both short-term and long-term cellular changes. By using immortalized GnRH-secreting neurons, we now show that, in vitro, Ca²⁺-dependent gene expression, proceeding via calcineurin and the transcription factor nuclear factor of activated T cells, is a key player controlling the chemomigratory potential of developing GnRH-secreting neurons. Furthermore, our data highlight the switch nature of this phosphatase, whose activation or inactivation guides cells to proceed from one genetic program to the next.