Abstract
ABSTRACTSegmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at boundaries and segment centres, in part mediated by Fgf20 signalling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.
Highlights
Development of the central nervous system (CNS) requires precise regulation of the differentiation of neuronal and glial cell types from neural progenitor cells
Single-cell profiling of the developing zebrafish hindbrain and surrounding tissues To further understand the progressive patterning of neurogenesis in the developing zebrafish hindbrain, we analysed the transcriptome of single cells at three developmental stages (Fig.1A, B): 16 hpf, 24 hpf and 44 hpf
Transcription factors temporally regulating hindbrain neurogenesis To illustrate developmental insights that can be extracted from the single cell RNA-Seq data, we focused on transcription factors (TFs) (AnimalTFDB3.0 database; Zhang et al, 2012) and inferred their potential contribution to hindbrain neurogenesis
Summary
Development of the central nervous system (CNS) requires precise regulation of the differentiation of neuronal and glial cell types from neural progenitor cells This is achieved through a network of cell-cell signaling and transcription factors that inhibit or promote cell differentiation and specify cell type along the dorsoventral and anteroposterior axes of the neural epithelium. Cell specification along the dorsoventral axis involves localised sources of Shh, BMP and Wnt signals that act in a concentrationdependent manner to regulate expression of specific transcription factors (Dessaud et al, 2008; Dessaud et al, 2007; Hikasa and Sokol, 2013; Ikeya et al, 1997; Lee and Jessell, 1999; Liem et al, 1997; Panhuysen et al, 2004; Timmer et al, 2002; Ulloa and Marti, 2010). It is essential that a pool of progenitor cells is maintained as a source of later-differentiating cells, and this is achieved by multiple mechanisms that inhibit differentiation
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