An immunocytochemical study of the development of central serotoninergic neurons in the chick embryo.

The development of central serotoninergic neurons in the chick embryo has been investigated immunocytochemically by utilizing an antiserum to serotonin (5-HT). Immunoreactive neurons are first detected in the brainstem on embryonic day 4 (E4, stage 23), days earlier than 5-HT systems have been detected previously by biochemical techniques. The earliest 5-HT-containing cells at E4 appear rostral to the pontine flexure, yet by E5, 5-HT neuronal groups are observed throughout the brainstem from just caudal to the mesencephalic flexure to the cervical flexure. During this and subsequent phases of development, two distinct patterns of cellular migration seem to be involved in the formation of the various 5-HT neuronal groups. One pattern involves a ventral migration of 5-HT cells, which appears dependent upon the directional guidance of midline radial processes (formed by floor plate cells) that extend across the neuroepithelium. The other pattern involves a lateral migration of cells, followed by an aggregation and rearrangement of 5-HT neurons into distinct subgroups or clusters. Through these patterns of migration most components of the 5-HT neuronal system can be recognized as early as E12, with the mature organization of the 5-HT cell groups occurring by E17. One unexpected finding was the comparatively late appearance (between E9 and E12) of 5-HT neurons in the paraventricular organ of the hypothalamus. Thus, in comparison to the initial observation of the majority of brainstem 5-HT neurons at E4 to E5, the hypothalamic 5-HT cells appear after a delay of between 5 and 7 days. Such differences illustrate the fact that neurons sharing a common neurotransmitter phenotype do not necessarily share the same developmental timetable for the expression of that particular phenotype, or they may undergo neurogenesis during considerably different periods of embryogenesis.