Abstract
Neural progenitors produce neurons whose identities can vary as a function of the time that specification occurs. Here, we describe the heterochronic specification of two photoreceptor (PhR) subtypes in the zebrafish pineal gland. We find that accelerating PhR specification by impairing Notch signaling favors the early fate at the expense of the later fate. Using in vivo lineage tracing, we show that most pineal PhRs are born from a fate-restricted progenitor. Furthermore, sister cells derived from the division of PhR-restricted progenitors activate the bone morphogenetic protein (BMP) signaling pathway at different times after division, and this heterochrony requires Notch activity. Finally, we demonstrate that PhR identity is established as a function of when the BMP pathway is activated. We propose a novel model in which division of a progenitor with restricted potential generates sister cells with distinct identities via a temporal asymmetry in the activation of a signaling pathway.
Highlights
The development of a functional nervous system requires the production of an amazing diversity of cell types
The expression of exorh and red cone opsin has been described in the developing and adult pineal gland using in situ hybridization [24,26], and the expression of PT, a green-sensitive photopigment that belongs to the so-called non-visual opsins, has been described using reverse transcription PCR (RT-PCR) [27,28]
We performed in situ hybridization against the endogenous opsins coupled with immunostaining for green fluorescent protein (GFP)/cyan fluorescent protein (CFP) in a previously described Tg(exorh:EGFP)ja1 transgene [29] or a transgenic reporter for the PT gene, Tg(-2.2parietopsin:CFP), that we established for this study
Summary
The development of a functional nervous system requires the production of an amazing diversity of cell types. Progenitors in the p2 domain of the spinal cord have the choice between the v2a and the v2b interneuron fate In this system, BMP and Notch cooperate to promote the v2b fate [8,9,10,11], with Notch acting to promote activation of the BMP pathway in the future v2b cell [5]. BMP and Notch cooperate to promote the v2b fate [8,9,10,11], with Notch acting to promote activation of the BMP pathway in the future v2b cell [5] These two pathways are involved in neural subtype specification in the zebrafish pineal gland but with the roles being reversed [6]; BMP operates first to promote responsiveness to Notch signaling during the choice between PhR and projection neuron (PN) fates
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