The generation of neurons from stem cells involves the activity of proneural basic helix-loop-helix (bHLH) proteins, but the mechanism by which these proteins irreversibly commit stem cells to neuronal differentiation is not known. Here we report that expression of the transcription factors Sox1, Sox2 and Sox3 (Sox1-3) is a critical determinant of neurogenesis. Using chick in ovo electroporation, we found that Sox1-3 transcription factors keep neural cells undifferentiated by counteracting the activity of proneural proteins. Conversely, the capacity of proneural bHLH proteins to direct neuronal differentiation critically depends on their ability to suppress Sox1-3 expression in CNS progenitors. These data suggest that the generation of neurons from stem cells depends on the inhibition of Sox1-3 expression by proneural proteins.
The prospect of using cell replacement therapies has raised the key issue of whether elucidation of developmental pathways can facilitate the generation of therapeutically important cell types from stem cells. Here we show that the homeodomain proteins Lmx1a and Msx1 function as determinants of midbrain dopamine neurons, cells that degenerate in patients with Parkinson's disease. Lmx1a is sufficient and required to trigger dopamine cell differentiation. An early activity of Lmx1a is to induce the expression of Msx1, which complements Lmx1a by inducing the proneural protein Ngn2 and neuronal differentiation. Importantly, expression of Lmx1a in embryonic stem cells results in a robust generation of dopamine neurons with a "correct" midbrain identity. These data establish that Lmx1a and Msx1 are critical intrinsic dopamine-neuron determinants in vivo and suggest that they may be essential tools in cell replacement strategies in Parkinson's disease.
The pattern of neuronal specification in the ventral neural tube is controlled by homeodomain transcription factors expressed by neural progenitor cells, but no general logic has emerged to explain how these proteins determine neuronal fate. We show that most of these homeodomain proteins possess a conserved eh1 motif that mediates the recruitment of Gro/TLE corepressors. The eh1 motif underlies the function of these proteins as repressors during neural patterning in vivo. Inhibition of Gro/TLE-mediated repression in vivo results in a deregulation of cell pattern in the neural tube. These results imply that the pattern of neurogenesis in the neural tube is achieved through the spatially controlled repression of transcriptional repressors-a derepression strategy of neuronal fate specification.
Aim The paper has four major objectives: (1) to determine whether diaspore mimics accurately represent dispersal dynamics of real diaspores in a free-flowing river; (2) to estimate distance travelled and reasons for stranding of floating diaspores along a free-flowing river;(3) to test if species composition and seedling recruitment vary with the ability of the riverbank to trap waterborne drift; and (4) to compare diaspore dispersal in a freeflowing river with that in a regulated river where current velocity has been reduced. LocationThe field work was conducted in two 7th-order boreal rivers in northern Sweden, the free-flowing Vindel River and the regulated Ume River. MethodsWe performed a series of dispersal experiments. We tested the usefulness wooden cubes of diaspore mimics for performing dispersal experiments by releasing cubes and achenes of Helianthus annuus and compare their dispersal patterns in the free-flowing Vindel River. We used the cubes to identify 50-m long sections along the river with different trapping capacity, i.e. the number of stranded diaspore mimics within a 50-m section. We then related the number of stranded diaspore mimics to the vascular plant flora, the proportions of species with long or short floating times (i.e. more than or less than 2 days, respectively), the number of seedlings, and to environmental variables within the sections. We also released wooden cubes in a run-of-river impoundment to determine the dispersal capacity of diaspores in a regulated river. ResultsThe cubes were useful as diaspore mimics. They dispersed similarly to achenes of H. annuus . The stranding pattern of diaspore mimics was significantly associated with water current. Species richness of vascular plants per 50-m section increased with the number of stranded mimics. Seedling recruitment, and the proportions of species with short-floating and long-floating diaspores, did not vary with the number of stranded mimics. The ability of a river to transport diaspores downstream was strongly reduced by impoundment. Main conclusionsWe conclude that patterns of species richness of riparian vegetation is in part determined by the ability of the riverbank to trap waterborne diaspores, but differences in floating ability among species did not affect the species composition along free-flowing rivers.
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