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J E Varley

Publications and source records attributed to J E Varley.

8 recordsLinked to original sources
PubMed2000

Expression and regulation of type I BMP receptors during early avian sympathetic ganglion development.

We have investigated the expression and regulation of the mRNAs for the type I BMP receptors, BMPR-IA and BMPR-IB, in quail embryos in vivo and in neural crest cultures in vitro. BMPR-IB mRNA was expressed in the primordial sympathetic ganglia at stage 17, soon after the first expression of Cash-1 mRNA, the avian homolog of the Drosophila transcription factor achaete-scute. BMP-4 mRNA was detected in the dorsal aorta at stage 17, coincident with BMPR-IB mRNA expression in the sympathetic ganglia. BMPR-IA mRNA was first expressed in the sympathetic ganglia at stage 18. Moreover, BMP-4 ligand mRNA was detected in the sympathetic ganglia starting at stage 18. BMPR-IA and BMPR-IB were differentially regulated in cultured neural crest cells. BMPR-IB was expressed in primary outgrowths of neural crest cells but was downregulated after primary outgrowths were harvested and replated in secondary cultures. In secondary cultures of neural crest cells, exogenous BMP-2 and BMP-4 increased the expression of BMPR-IA but decreased the expression of BMPR-IB. The expression of both type I BMP receptors was inhibited by exogenous TGF-beta1. Our results suggest distinct roles for BMPR-IA and BMPR-IB in the development of the sympathoadrenal phenotype from cells of the neural crest.

Amino Acid Sequence↗
PubMed1998

Expression of a constitutively active type I BMP receptor using a retroviral vector promotes the development of adrenergic cells in neural crest cultures.

Previous work has demonstrated that the bone morphogenetic proteins (BMP)-2, BMP-4, and BMP-7 can promote the development of tyrosine hydroxylase (TH)-positive and catecholamine-positive cells in quail trunk neural crest cultures. In the present work, we showed that mRNA for the type I bone morphogenetic protein receptor IA (BMPR-IA) was present in neural crest cells grown in the absence or presence of BMP-4. We have used a replication-competent avian retrovirus to express a constitutively active form of BMPR-IA in neural crest cells in culture. Cultures grown in the absence of BMP-4 and infected with retrovirus containing a construct encoding this activated BMPR-IA developed five times more TH-immunoreactive and catecholamine-positive cells than uninfected control cultures or cultures infected with virus bearing the wild-type BMPR-IA cDNA. The number of TH-positive cells which developed was dependent on the concentration of virus bearing the activated receptor cDNA used in the experiments. Most TH-positive cells which developed also contained viral p19 protein. Total cell number was not affected by infection with the virus containing the activated receptor construct. The effect of the activated receptor was phenotype-specific since infection with the virus bearing the activated receptor cDNA did not alter the number or morphology of microtubule-associated protein (MAP)2-immunoreactive cells, which are distinct from the TH-positive cell population. These findings are consistent with the observation that MAP2-positive cells are not affected by the presence of BMP-4. Taken together, these results suggest that activity of BMPR-IA is an important element in promoting the development of the adrenergic phenotype in neural crest cultures.

Adrenergic Fibers↗
PubMed1996

BMP-2 and BMP-4, but not BMP-6, increase the number of adrenergic cells which develop in quail trunk neural crest cultures.

The bone morphogenetic proteins (BMPs) are members of the TGF beta superfamily of growth factors. We have investigated the effects of BMP-2, BMP-4, and BMP-6 on the development of quail trunk neural crest cells in tissue culture. The presence of human recombinant BMP-2 or BMP-4 resulted in a dramatic increase in the number of tyrosine hydroxylase (TH)-immunoreactive cells which developed after 7 days in vitro. In contrast, BMP-6 showed little or no effect. Total cell number was not altered significantly by BMP-2, BMP-4, or BMP-6. However, in the presence of BMP-2 and BMP-4, but not BMP-6, the fraction of the cell population that became melanocytes was reduced to about two-thirds the control value. Addition of BMP-2 and BMP-4 also increased the number of Islet-1-immunoreactive and Hu-immunoreactive cells, but the magnitude of these increases was less than that observed for the TH-immunoreactive cell population. The Islet-1-immunoreactive cells were a subset of the TH-immunoreactive cells, while the Hu-positive cells were distinct from the TH-immunoreactive population. Analysis using bromodeoxyuridine labeling indicated that the increased numbers of TH-immunoreactive cells observed in the presence of BMP-2 and BMP-4 were not due to an increased rate of cell division in committed TH precursors. Further experiments, in which cultures were initiated from single cells, showed that the presence of BMP-2 resulted in colonies containing numerous catecholamine-positive cells without altering the overall number of colonies which survived and developed. In summary, our findings indicate that BMP-2 and BMP-4 are potent regulators of the adrenergic development of avian trunk neural crest cells.

Adrenergic Fibers↗
PubMed1995

Number of adrenergic and islet-1 immunoreactive cells is increased in avian trunk neural crest cultures in the presence of human recombinant osteogenic protein-1.

OP-1, also known as BMP-7, is a member of the TGF-beta 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 catecholamine-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-beta 1 decreased adrenergic cell number. When OP-1 and TGF-beta 1 were added simultaneously, TGF-beta 1 antagonized the OP-1-mediated increase in adrenergic cell number in a dose-dependent manner.

Animals↗
PubMed1965

The autistic child.

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Autistic Disorder↗