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. 2017 Apr 12;5(2):4. doi: 10.3390/jdb5020004

Figure 2.

Figure 2

Dynamics of Shh source cells along with neural patterning progression in amniotes (a) and zebrafish (b). (a) Shh, first provided by the notochord (t1), induces a low-dose response program in the neural tube revealed by Olig2 expression in ventral progenitor cells. Formation of this pre-pattern is observed over eight days of development (E8) in the mouse embryo [19,26,29]. As development proceeds (t1–t3), increasing doses of Shh are progressively provided by the notochord. In response to the resulting activation of Shh signalling in the receiving field, ventral progenitor cells upregulate Nkx2.2 and Foxa2 (t2). Expression of these high threshold Shh responsive genes progressively extends dorsally (t3) and Olig2 is downregulated in the ventral-most progenitor cells due to the repressive activity of Nkx2.2. In parallel, Shh expression is activated in ventral midline cells (t3), thus completing MFP cell differentiation. In these cells, Shh signalling is downregulated and Nkx2.2 expression is turned off. At that time, patterning of neuron-producing domains is achieved. The t2t3 period of development corresponds roughly to the period between the ages of E1.5-E2 and E8.5-E9.5 in chicks and mice, respectively [19,26,28,29,60]. From that time, MFP becomes the main provider of Shh required to maintain progenitor domains. This is paralleled by a general decrease of Shh signalling activity in ventral progenitor cells while they start generating neurons [20,27]. After a period of several days (t4), ventral progenitor cells co-expressing Nkx2.2 and Foxa2 activate Shh expression to form the LFP. This is associated with a decay of Shh signalling in these cells. At that time, Shh signalling is activated in dorsal adjacent progenitor cells that subsequently upregulate Nkx2.2. This change in pattern organization leads to formation of a novel progenitor domain populated by Olig2/Nkx2.2-coexpressing cells that change their fate to generate glial cells. t4 corresponds to E5.5 in chicks and E11.5 in mice [42,43]. (b) At initiation of neural tube patterning in zebrafish (t1), Hedgehog ligands are provided by the notochord but also by MFP cells. The time course of Olig2 and Nkx2.2 expression in ventral progenitor cells is conserved. Pattern formation of ventral progenitor domains (t1t2) takes place over a short period of time, from 14 to 16 hours post-fertilization (hpf) [43,61,62]. After a period of approximately one day (t3), Shh expression expands laterally into the Nkx2.2-expressing domain to form the LFP and the subsequent reorganization of the ventral patterning that is in place from 36 hpf in zebrafish [40,43].