Major transcriptome re-organisation and abrupt changes in signalling, cell cycle and chromatin regulation at neural differentiation in vivo.
Bottom Line: We show that these changes are conserved across species and provide biological evidence for reduced proteasome efficiency and a novel lengthening of S phase.We further demonstrate that transcription of one such gene, HDAC1, is dependent on FGF signalling, making a novel link between signals that control neural differentiation and transcription of a core regulator of chromatin organisation.Our work implicates new signalling pathways and dynamics, cellular processes and epigenetic modifiers in neural differentiation in vivo, identifying multiple new potential cellular and molecular mechanisms that direct differentiation.
Affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.Show MeSH
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Mentions: The spinal cord is generated progressively as cells leave the caudal region of the elongating body axis (Wilson et al., 2009), such that the temporal steps of neural differentiation become spatially separated along the head to tail axis. At key stages, it is therefore possible to isolate near-adjacent cell populations from the same embryo in distinct differentiation states (Fig. 1A). Cells in the caudal lateral epiblast adjacent to the primitive streak [also known as the stem zone (SZ) in the chick] (Wilson et al., 2009) express both early neural and mesodermal genes (Delfino-Machín et al., 2005), and there is evidence in the mouse that this cell population includes axial stem cells (Tzouanacou et al., 2009; Wilson et al., 2009). Other cells in the stem zone will gastrulate to form the paraxial mesoderm or remain in the epiblast cell sheet and become neural progenitors (Delfino-Machín et al., 2005). These latter cells form a new region called the preneural tube (PNT), which is flanked by unsegmented presomitic mesoderm; this represents an early neural progenitor state that can be induced by FGF signalling to revert back to a multi-potent SZ state (Diez del Corral et al., 2002). Cells in the PNT also undergo morphogenetic movements to close the neural tube. Rostral to this, the closed caudal neural tube (CNT) is flanked by somites and is an early site of co-expression of all three Sox1B genes, which are characteristic of neural progenitors (Delfino-Machín et al., 2005; Stavridis et al., 2010), and of key ventral patterning genes (Diez del Corral et al., 2003). The CNT contains the first few neurons and exposure to FGF cannot revert this tissue to a multi-potent SZ state (Diez del Corral et al., 2002). The transition from the PNT to the CNT thus involves commitment to a neural fate and we have demonstrated that this is regulated by a switch from FGF to retinoid signalling (Diez del Corral et al., 2003; Stavridis et al., 2010). More advanced neuroepithelium is then located in more rostral neural tube (RNT), in which neuronal differentiation is ongoing and dorsoventral pattern is refined. Here, we use the Affymetrix GeneChip chicken genome microarray to compare the transcriptomes of these spatially distinct cell populations from the elongating neural axis.Fig. 1.
Affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.