Context-dependent neuronal differentiation and germ layer induction of Smad4−/− and Cripto−/− embryonic stem cells

TGF-β, Neuronal Stem Cells and Glioblastoma

“…However, ES cell-derived neurogenesis does not entirely depend on functional Smad4, indicating that other factors, such as cell-cell contact, the cellular environment, and other signaling molecules, are involved in the process (Sonntag et al, 2005). The existence of multipotential, self-renewing NSCs in adult mammalian brain re-emerged in the past decade (Gage, 2000;Anderson, 2001;Temple, 2001;Gage, 2002;, confirming an earlier report on neurogenesis in the adult brain (Gross, 2000).…”

“…In the stem cells, Smad4 is dispensable for neuronal specification (Sonntag et al, 2005) implicating that there are other mechanisms that compensate for some of TGF-b's signaling impact. As for ELF, in younger stem cell populations, its contribution in propagating TGF-b signals would allow the cells to divide and differentiate at a normal rate, while its deficiency may be conducive for cell proliferation and, therefore, maintaining the stem cell-like properties.…”

“…Rat olfactory cell neurogenesis appears to be critically dependent upon FGF2 and TGF-b sequentially (Kawauchi et al, 2004). Blocking Smad4 might not be sufficient to block mesenchymal fate in embryonic stem (ES) cells, but does promote neuronal fate (Sonntag et al, 2005). Spinal cord neurogenesis is promoted by inhibition of BMP signaling through expression of Noggin (Setoguchi et al, 2004).…”

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

“…We confirmed the coexpression of FOXA2 and GIRK2 in SNc tissue that contains A9 dopaminergic neurons but not in the VTA, which contains A10 dopaminergic neurons. GIRK2/FOXA2 double-positive cells have not been induced from other stem cell sources using existing protocols (44)(45)(46), except for one that manipulates both the sonic hedgehog and WNT signaling pathways (43,47). Recent studies of fetal tissue engrafting in patients with PD or PD model rats have shown that A9 dopaminergic neurons are determinants of successful functional recovery (16,48) and decreased dyskinesia (49) and that they are associated with well-organized synaptic connectivity (16).…”

Nodal-dependant Cripto signaling in ES cells: from stem cells to tumor biology

“…Interestingly, it has been recently described that Cripto À/À ES cells show enhanced neurogenesis compared to wild-type ES cells (Sonntag et al, 2005) following the five stage-neuronal differentiation protocol, a method described for efficient generation of dopaminergic and serotonergic neurons from ES cells (Lee et al, 2000;Chung et al, 2002). However, multilineage cell types have also been found in Cripto À/À ES cells, thus suggesting that loss of function of Cripto is not sufficient to result in a 'default' neural pathway, at least in this in vitro paradigm (Sonntag et al, 2005).…”