For example, cell-based assays analogous to key neurodevelopmental processes such as neural precursor commitment, neuronal and glial cell migration, proliferation, differentiation, synaptogenesis, neurite outgrowth, functional measurements of electrical activity, ratio between neuronal and glial cells provide a reliable mechanistic insight into a potential DNT's effects (Bal-Price et al. 2012 ).
Epithelial cells in the thymic cortex are responsible for the attraction of T cell precursors, commitment to the T cell lineage, expansion of immature double negative (DN) thymocytes and positive selection of double positive (DP) thymocytes [2].
To elucidate whether Lhx2 expression affects committed EryP precursors and/or commitment to this lineage from the hemangioblast we added dox to day 3 and 4 EBs, when commitment to this lineage occur, and replated the day 6 EBs without dox when commitment to this lineage has normally occurred.
RA-induced differentiation of NT2 cells proceeds through distinct phases of neural commitment, precursor expansion and terminal differentiation to neurons and astroglia [32] and analysis of neural gene markers shows a characteristic temporal and spatial pattern of gene expression similar to neuroepithelial precursors during in vivo neurogenesis [33], [34].
By asymmetric cell divisions resulting daughter cells form lineage restricted precursors with increasing commitment, finally leading to terminally differentiated postmitotic cell types [ 8, 9].
Irradiation may have reduced neuronal differentiation of mitotic stem cells, as shown by Steele and Lange [45], possibly by delaying the commitment of precursor cells to neuronal fate, as recently reported by our collaborators (Dranovsky, Hen et al., Science, in press).
This well characterized cell system is a valuable in vitro model of neurogenesis, in which these "surrogate" stem cells undergo, in response to RA treatment, expansion of precursor pool, neural fate commitment and terminal differentiation to neurons and astroglia [32], [33], [47], [48].
Formation of the primordial vascular network results from the commitment by precursor cells (haemangioblasts) to form endothelial cells, rather than haematopoietic stem cells.
A single transcription factor, Oct4, was shown to generate haematopoietic stem cells from fibroblasts that could be further differentiated into various myeloid cell types, suggesting functionality of all intermediate precursor states and lineage commitment steps (Szabo et al, 2010).
In total, 31 ESTs encoded cyclotide precursors, representing a distinct commitment of 2.8% of the O. affinis transcriptome to cyclotide biosynthesis.
The data described above suggest that precocious PU.1 expression in haematopoietic precursors can drive haematopoietic commitment through the activation of a TF network.
