title: Crosstalk among electrical activity, trophic factors and morphogenetic proteins in the regulation of neurotransmitter phenotype specification.
abstract: Morphogenetic proteins are responsible for patterning the embryonic nervous system by enabling cell proliferation that will populate all the neural structures and by specifying neural progenitors that imprint different identities in differentiating neurons. The adoption of specific neurotransmitter phenotypes is crucial for the progression of neuronal differentiation, enabling neurons to connect with each other and with target tissues. Preliminary neurotransmitter specification originates from morphogen-driven neural progenitor specification through the combinatorial expression of transcription factors according to morphogen concentration gradients, which progressively restrict the identity that born neurons adopt. However, neurotransmitter phenotype is not immutable, instead trophic factors released from target tissues and environmental stimuli change expression of neurotransmitter-synthesizing enzymes and specific vesicular transporters modifying neuronal neurotransmitter identity. Here we review studies identifying the mechanisms of catecholaminergic, GABAergic, glutamatergic, cholinergic and serotonergic early specification and of the plasticity of these neurotransmitter phenotypes during development and in the adult nervous system. The emergence of spontaneous electrical activity in developing neurons recruits morphogenetic proteins in the process of neurotransmitter phenotype plasticity, which ultimately equips the nervous system and the whole organism with adaptability for optimal performance in a changing environment.
authors.affiliation: Department of Physiology & Membrane Biology and Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children, University of California Davis School of Medicine, 2425 Stockton Blvd, Sacramento, CA 95817, United States. Electronic address: lnborodinsky@ucdavis.edu.
authors.forename: Laura N
authors.initials: LN
authors.lastname: Borodinsky
authors.affiliation: Department of Physiology & Membrane Biology and Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children, University of California Davis School of Medicine, 2425 Stockton Blvd, Sacramento, CA 95817, United States.
authors.forename: Yesser H
authors.initials: YH
authors.lastname: Belgacem
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D020013:Calcium Signaling; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D004560:Electricity; D018698:Glutamic Acid / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D018377:Neurotransmitter Agents; D012701:Serotonin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine
keywords: Calcium signaling; Morphogenetic proteins; Neurotransmitter phenotype specification and plasticity; Sonic hedgehog; Spontaneous electrical activity; Target-derived trophic factors