The mouse dorsal raphe nucleus as understood by temporal Fgf8 lineage analysis

Fgf8 is expressed transiently during embryogenesis at the midbrain-hindbrain border, an area that gives rise to a variety of neuronal populations including the dorsal raphe (DR) nucleus. Using an inducible Fgf8-cre allele, we identified the populations of neurons defined by Fgf8 lineage at different stages of development. When Fgf8-cre expression is induced at embryonic day 7.5 (T-E7.5), in the adult the entire DR and part of the median raphe (MnR) have Fgf8 lineage. When induced at later timepoints, Fgf8 lineage progressively ebbs from the caudal and ventral aspect of this domain, particularly on the midline. Successively excluded from Fgf8- lineage at T-E9.5 are serotonin neurons in the MnR and caudal-intrafascicular DR, followed at T-E11.5 by ventral-middle and caudal-dorsal DR. The last to show Fgf8 lineage are those serotonin neurons in the lateral wings and those at the rostral-dorsal pole of DR nucleus. Thus, the temporal succession of Fgf8 lineage correlates with organizational features of serotonin neurons in these nuclei.