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

Abstract

OP-1, also known as BMP-7, is a member of the TGF-P 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. 179116123). 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-PI decreased adrenergic cell number. When OP-1 and TGF-P1 were added simultaneously, TGF-P1 antagonized the OP-1-mediated increase in adrenergic cell number in a dose-dependent manner. 0 1995 Wiley-Liss, Inc.

Multiple Endocrine Regulation by Bone Morphogenetic Protein System

“…For instance, BMP-4 and BMP-7 are expressed in the dorsal aorta and direct sympathetic neuronal differentiation into the adrenergic characteristics [80]. BmP-4 and BMP-7 induce a tyrosine hydroxylase (TH)-immunoreactive adrenergic phenotype in cultures of avian neural crest cells [81,82]. We also found that BMP-4 and BMP-7 induce catecholamine production in the presence of mineralocorticoid in adrenal medullar cells.…”

Molecular control of ciliary neuron development: BMPs and downstream transcriptional control in the parasympathetic lineage

“…Noggin-treatment also affected the development of the eye, whereas control embryos, receiving control CHO cells, had normal sized eyes and the ciliary ganglion was present. To investigate whether the effects on ciliary neurons are an indirect result of the missing (Varley et al, 1995;Reissmann et al, 1996;Shah et al, 1996;Schneider et al, 1999) and parasympathetic ciliary neurons (the present study). The differential expression of the BMP-downstream transcription factor dHand suggests that sympathetic and ciliary neuron precursors display differences that determine BMP downstream signaling and in turn neuron identity (illustrated by the different shading of sympathetic and parasympathetic precursor cells).…”

“…Sympathetic neuron generation is initiated by signals from the midline structures when neural crest precursor cells aggregate to form sympathetic ganglion primordia. Major components of these signals are BMP family members, which are essential and sufficient to induce the generation of sympathetic neurons from neural crest cells in vitro and in vivo (Varley et al, 1995;Reissmann et al, 1996;Shah et al, 1996;Shah and Anderson, 1997;Schneider et al, 1999). BMP2/4 and 7 are produced by the dorsal aorta before and during sympathetic neuron development (Reissmann et al, 1996;Shah et al, 1996).…”

Mitogenic and anti‐proliferative signals for neural crest cells and the neurogenic action of TGF‐β1

“…Stimulation of avian adrenergic differentiation by TGF-b and related proteins has been described by Howard and Gershon (1993;TGF-b1), Varley et al (1995;osteogenic protein-1) and Varley and Maxwell (1966;BMP-2 and BMP-4). Our data are in agreement with these reports and extend them by the additional observation of enhanced expression of a sensory neuron marker.…”