Fgf Signaling Governs the Differentiation of Parapineal Neurons in Zebrafish

Abstract

Parapineal precursors arise from the medially located pineal complex anlage and migrate to the left side of the brain. Published data implicates Fgf8a in the migration of parapineal cells away from the midline of the pineal anlage. However, the potential role for Fgf8a during the acquisition of parapineal cell fate was not addressed. We have found that Fgf8a regulates a fate decision among specified parapineal precursors that occurs just prior to the initiation of leftward migration. Attenuation of Fgf signaling results in the loss of parapineal cells and the gain of additional cone cells. Data obtained from the combined loss of Flh and Fgf8a, as well as cell fate analysis, shows that in the absence of Fgf signaling, parapineal precursors differentiate as cone photoreceptors rather than parapineal cells. Furthermore, Fgf8a acts permissively to promote parapineal fate in conjunction with the transcription factor Tbx2b, but acts by itself to either block cone photoreceptor fate or promote parapineal differentiation. This cell fate change is independent of Bmp signaling, which promotes the formation of pineal photoreceptors. Instead, parapineal cell differentiation likely requires the two transcription factors, Lhx2b and Lhx9, which are responsive to Fgf signaling and are involved in parapineal formation.