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David C. Rueger

Bio: David C. Rueger is an academic researcher. The author has contributed to research in topics: Neural crest & Cell. The author has an hindex of 1, co-authored 1 publications receiving 112 citations.

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TL;DR: The OP‐1‐mediated increase in adrenergic cell number most likely occurs as a result of the enhanced survival of a subpopulation of adrenergic precursors or an increase in their probability of Adrenergic differentiation, but not by increasing the mitotic rate of adren allergic precursor or adrenergic cells themselves.
Abstract: OP-1, also known as BMP-7, is a member of the TGF-β superfamily of proteins and was originally identified on the basis of its ability to induce new bone formation in vivo. OP-1 mRNA is found in the developing kidney and adrenal gland as well as in some brain regions (Ozkaynak et al. [1991] Biochem. Biophys. Res. Commun. 179:116–123). We have tested the effect of recombinant human OP-1 on quail trunk neural crest cultures. The number of catechol-amine-positive cells which developed after 7 days in vitro in the presence of OP-1 was increased in a dose-dependent manner, with a greater than 100-fold maximal stimulation observed. The increase in the number of catecholamine-positive cells in the presence of OP-1 was paralleled by an increase in the number of tyrosine hydroxylase (TH)-positive cells. In contrast, total and melanocyte cell number were unaffected by the presence of OP-1. The number of Islet-1-immunoreactive cells was also increased by OP-1, but to only about half the value seen for TH. Double label experiments revealed these Islet-1-positive cells were a subset of the TH-positive cells. Inhibitors of DNA synthesis prevented the OP-1-mediated increase in adrenergic cell number, indicating that OP-1 does not act on a postmitotic cell population. However, labeling studies with bromodeoxyuridine indicated that OP-1 did not increase the proportion of the cell population engaged in DNA synthesis. Thus, the OP-1-mediated increase in adrenergic cell number most likely occurs as a result of the enhanced survival of a subpopulation of adrenergic precursors or an increase in their probability of adrenergic differentiation, but not by increasing the mitotic rate of adrenergic precursors or adrenergic cells themselves. In contrast to OP-1, TGF-β1 decreased adrenergic cell number. When OP-1 and TGF-β1 were added simultaneously, TGF-β1 antagonized the OP-1-mediated increase in adrenergic cell number in a dose-dependent manner. �1995 Wiley-Liss, Inc.

113 citations


Cited by
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Journal ArticleDOI
03 May 1996-Cell
TL;DR: It is demonstrated that bone morphogenic protein 2 (BMP2) induces the basic-helix-loop- Helix protein MASH1 and neurogenesis in neural crest stem cells and some smooth muscle differentiation is also observed in BMP2.

847 citations

Journal ArticleDOI
TL;DR: Gremlin belongs to a novel gene family that includes the head-inducing factor Cerberus and the tumor suppressor DAN and it is proposed that Gremlin, Cerberus, and DAN control diverse processes in growth and development by selectively antagonizing the activities of different subsets of the TGF beta ligands.

710 citations

Journal ArticleDOI
TL;DR: Analysis of expression patterns in the central nervous system and heart of the developing mouse embryo suggests that BMP family members can functionally substitute for BMP7 at sites where they colocalize in vivo.
Abstract: BMP7 is expressed at diverse sites in the developing mouse embryo, including visceral endoderm, notochord, heart, eye, kidney, and bone. A null mutation in BMP7 results in defects largely confined to the developing kidney and eye. To examine whether other bone morphogenetic protein (BMP) family members potentially substitute for BMP7 in mutant embryos, thereby restricting the observed defects, we analyzed the expression patterns of BMP2 through BMP7 in wild-type and mutant tissues. In the central nervous system and heart, which develop normally in the absence of BMP7 signaling, expression domains of other BMP family members completely overlap with that of BMP7. The variable expressivity of the eye defect correlates with partially overlapping BMP4 and BMP7 expression domains during early eye induction. The loss of BMP7 signaling in the kidney results in apoptosis in the metanephric mesenchyme, a cell population that exclusively expresses BMP7. Thus, tissue defects observed in BMP7 deficient embryos are restricted to cell populations exclusively expressing BMP7. These data suggest that BMP family members can functionally substitute for BMP7 at sites where they colocalize in vivo.

467 citations

Journal ArticleDOI
TL;DR: The data demonstrate that isolated mammalian NCSCs uniformly possess SA lineage capacity and further suggest that oxygen levels can influence cell fate and suggests that neural stem cells may exhibit a conserved response to reduced oxygen levels.
Abstract: Isolated neural crest stem cells (NCSCs) differentiate to autonomic neurons in response to bone morphogenetic protein 2 (BMP2) in clonal cultures, but these neurons do not express sympathoadrenal (SA) lineage markers. Whether this reflects a developmental restriction in NCSCs or simply inappropriate culture conditions was not clear. We tested the growth and differentiation potential of NCSCs at ∼5% O_2, which more closely approximates physiological oxygen levels. Eighty-three percent of p75^+P_0 ^− cells isolated from embryonic day 14.5 sciatic nerve behaved as stem cells under these conditions, suggesting that this is a nearly pure population. Furthermore, addition of BMP2 plus forskolin in decreased oxygen cultures elicited differentiation of thousands of cells expressing tyrosine hydroxylase, dopamine-β-hydroxylase, and the SA lineage marker SA-1 in nearly all colonies. Such cells also synthesized and released dopamine and norepinephrine. These data demonstrate that isolated mammalian NCSCs uniformly possess SA lineage capacity and further suggest that oxygen levels can influence cell fate. Parallel results indicating that reduced oxygen levels can also promote the survival, proliferation, and catecholaminergic differentiation of CNS stem cells (Studer et al., 2000) suggests that neural stem cells may exhibit a conserved response to reduced oxygen levels.

424 citations

Journal ArticleDOI
TL;DR: Bone morphogenetic proteins act on more lineage-restricted embryonic CNS progenitor cells to promote regional neuronal survival and cellular differentiation and induce selective apoptosis of discrete rhombencephalic neural crest-associated cellular populations.

415 citations