Abstract
BackgroundThe dorsal domain of the neural tube is an excellent model to investigate the generation of complexity during embryonic development. It is a highly dynamic and multifaceted region being first transiently populated by prospective neural crest (NC) cells that sequentially emigrate to generate most of the peripheral nervous system. Subsequently, it becomes the definitive roof plate (RP) of the central nervous system. The RP, in turn, constitutes a patterning center for dorsal interneuron development. The factors underlying establishment of the definitive RP and its segregation from NC and dorsal interneurons are currently unknown.ResultsWe performed a transcriptome analysis at trunk levels of quail embryos comparing the dorsal neural tube at premigratory NC and RP stages. This unraveled molecular heterogeneity between NC and RP stages, and within the RP itself. By implementing these genes, we asked whether Notch signaling is involved in RP development. First, we observed that Notch is active at the RP-interneuron interface. Furthermore, gain and loss of Notch function in quail and mouse embryos, respectively, revealed no effect on early NC behavior. Constitutive Notch activation caused a local downregulation of RP markers with a concomitant development of dI1 interneurons, as well as an ectopic upregulation of RP markers in the interneuron domain. Reciprocally, in mice lacking Notch activity, both the RP and dI1 interneurons failed to form and this was associated with expansion of the dI2 population.ConclusionsCollectively, our results offer a new resource for defining specific cell types, and provide evidence that Notch is required to establish the definitive RP, and to determine the choice between RP and interneuron fates, but not the segregation of RP from NC.
Highlights
The dorsal domain of the neural tube is an excellent model to investigate the generation of complexity during embryonic development
Defining the mechanisms that generate a sequence of specialized cell types and further coordinate their functions is critical for understanding organ development
Differential gene expression analysis revealed significant upregulation of 1243 and downregulation of 1068 genes in roof plate (RP) when compared to neural crest (NC), respectively, providing a rich data source for further functional analysis (Fig. 1b, c and Additional file 2: Table S1 and Additional file 3: Table S2)
Summary
The dorsal domain of the neural tube is an excellent model to investigate the generation of complexity during embryonic development It is a highly dynamic and multifaceted region being first transiently populated by prospective neural crest (NC) cells that sequentially emigrate to generate most of the peripheral nervous system. It becomes the definitive roof plate (RP) of the central nervous system. The dorsal neural tube (NT) epithelium is an excellent system to tackle these questions as it is a highly dynamic structure in both time and space [1] It is transiently populated by premigratory neural crest (NC) cells. The RP acts as a neural patterning center that secretes growth factors of the bone morphogenetic protein (BMP) and Wnt families, both crucial for dorsal interneuron development [7,8,9,10,11,12,13,14], and for proliferation of ependymal cells at later stages [15, 16]
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