Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lineage diversification in the vertebrate neural crest may occur via instructive signals acting on pluripotent cells, and/or via early specification of subpopulations towards particular lineages. Mesencephalic neural crest cells normally form cholinergic parasympathetic neurons in the ciliary ganglion, while trunk neural crest cells normally form both catecholaminergic and cholinergic neurons in sympathetic ganglia. In contrast to trunk neural crest cells, mesencephalic neural crest cells apparently fail to express the catecholaminergic transcription factor dHAND in response to BMPs in the head environment. Here, we show that migrating quail mesencephalic neural crest cells grafted into the trunk of host chick embryos colonise the sympathetic ganglia. While many express dHAND and form tyrosine hydroxylase (TH)-positive catecholaminergic neurons, the proportion that expresses either dHAND or TH is significantly smaller than that of quail trunk neural crest cells under the same conditions. Furthermore, the proportion of quail mesencephalic neural crest cells that is TH+ in the sympathetic ganglia decreases with time, while the proportion of TH+ quail trunk neural crest-derived cells increases. Thus, a subset of mesencephalic neural crest cells fails to express dHAND or TH in the sympathetic ganglia, while a further subset initiates but fails to maintain TH expression. Taken together, our results suggest that a subpopulation of migrating mesencephalic neural crest cells is refractory to catecholaminergic differentiation signals in the trunk. We suggest that this heterogeneity, together with local signals that repress catecholaminergic differentiation, may ensure that most ciliary neurons adopt a cholinergic fate.
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PMID:Restricted response of mesencephalic neural crest to sympathetic differentiation signals in the trunk. 1564 70

Human embryonic stem cells (hESCs) have been directed to differentiate into neuronal cells using many cell-culture techniques. Central nervous system cells with clinical importance have been produced from hESCs. To date, however, there have been no definitive reports of generation of peripheral neurons from hESCs. We used a modification of the method of Sasai and colleagues for mouse and primate embryonic stem cells to elicit neuronal differentiation from hESCs. When hESCs are cocultured with the mouse stromal line PA6 for 3 weeks, neurons are induced that coexpress (a) peripherin and Brn3a, and (b) peripherin and tyrosine hydroxylase, combinations characteristic of peripheral sensory and sympathetic neurons, respectively. In vivo, peripheral sensory and sympathetic neurons develop from the neural crest (NC). Analysis of expression of mRNAs identified in other species as NC markers reveals that the PA6 cells induce NC-like cells before neuronal differentiation takes place. Several NC markers, including SNAIL, dHAND, and Sox9, are increased at 1 week of coculture relative to naive cells. Furthermore, the expression of several NC marker genes known to be downregulated upon in vivo differentiation of NC derivatives, was observed to be present at lower levels at 3 weeks of PA6-hESC coculture than at 1 week. Our report is the first on the expression of molecular markers of NC-like cells in primates, in general, and in humans, specifically. Our results suggest that this system can be used for studying molecular and cellular events in the almost inaccessible human NC, as well as for producing normal human peripheral neurons for developing therapies for diseases such as familial dysautonomia.
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PMID:Generation of peripheral sensory and sympathetic neurons and neural crest cells from human embryonic stem cells. 1588 33