Maternal serotonin is crucial for murine embryonic development.
The early appearance of serotonin and its receptors during prenatal development, together with the many effects serotonin exerts during CNS morphogenesis, strongly suggest that serotonin influences the development and maturation of the mammalian brain before it becomes a neuromodulator/neurotransmitter. Sites of early serotonin biosynthesis, however, have not been detected in mouse embryos or extraembryonic structures, suggesting that the main source of serotonin could be of maternal origin. This hypothesis was tested by using knockout mice lacking the tph1 gene, which is responsible for the synthesis of peripheral serotonin. Genetic crosses were performed to compare the phenotype of pups born from homozygous and heterozygous mothers. Observations provide the first clear evidence that (i) maternal serotonin is involved in the control of morphogenesis during developmental stages that precede the appearance of serotonergic neurons and (ii) serotonin is critical for normal murine development. Most strikingly, the phenotype of tph1-/- embryos depends more on the maternal genotype than on that of the concepti. Consideration of the maternal genotype may thus help to clarify the influence of other genes in complex diseases, such as mental illness.
Côté
Francine
F
Université Pierre et Marie Curie, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS, Unité Mixte de Recherche 7091, Hôpital de la Pitié Salpêtrière, Paris, France. cote@chups.jussieu.fr
Fligny
Cécile
C
Bayard
Elisa
E
Launay
Jean-Marie
JM
Gershon
Michael D
MD
Mallet
Jacques
J
Vodjdani
Guilan
G
D000818:Animals; D047108:Embryonic Development; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D010661:Phenylketonurias / Q000209:etiology; D012333:RNA, Messenger / Q000032:analysis; D012701:Serotonin / Q000502:physiology*; D015398:Signal Transduction; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000502:physiology
D012333:RNA, Messenger; D012701:Serotonin; C487801:Tph1 protein, mouse; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase