Regulation by serotonin of tooth-germ morphogenesis and gene expression in mouse mandibular explant cultures

Moiseiwitsch, Julian; Raymond, John R.; Tamir, Hadassah; Lauder, Jean M.

doi:10.1016/s0003-9969(98)00067-3

Cited by 35 publications

(41 citation statements)

References 28 publications

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“…These sites appear to protect the underlying mesenchyme from exposure to inappropriate levels of 5-HT, as indicated by patterns of cell death and malformations, caused by exposure of cultured mouse embryos to selective 5-HT reuptake inhibitors (SSRIs), like fl uoxetine (Prozac) and sertraline (Zoloft) [Shuey et al, 1992]. As shown in a variety of in vitro models, 5-HT acts as a dose-dependent growth regulatory signal for craniofacial cells, regulating neural crest migration [Moiseiwitsch and Lauder, 1995], mesenchymal cell proliferation [Bhasin et al, 2004b;Buznikov et al, 2001;Nebigil et al, 2000], tooth germ development [Moiseiwitsch and Lauder, 1996], and expression of growth factors and extracellular matrix molecules, including those of the cartilage matrix [Lambert and Lauder, 1999;Lambert et al, 2001;Moiseiwitsch and Lauder, 1997;Moiseiwitsch et al, 1998]. Serotonin carries out these diverse developmental functions by activating different 5-HT receptor subtypes [Buznikov et al, 2001;Lambert et al, 2001], including 5-HT 2 receptors [Bhasin et al, 2004a, b;Lauder et al, 2000].…”

Section: Serotonergic Regulation Of Mouse Craniofacial Developmentmentioning

confidence: 99%

“…Expression of 5-HT 3 receptors in regions of active chondrogenesis in the embryonic craniofacial region [Tecott et al, 1995] suggests that these receptors may also play roles in craniofacial skeletal development. This possibility is supported by the ability of 5-HT 3 receptor ligands to alter expression of cartilage proteoglycan core protein in mandibular micromass and organotypic cultures [Moiseiwitsch and Lauder, 1997;Moiseiwitsch et al, 1998]. The importance of both 5-HT 2 and 5-HT 3 receptors for embryonic craniofacial development is further indicated by the potent teratogenetic activity of antagonists for these receptors in cultured mouse embryos [Lauder et al, 1994[Lauder et al, , 2000.…”

Section: Serotonergic Regulation Of Mouse Craniofacial Developmentmentioning

confidence: 99%

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Of Minds and Embryos: Left-Right Asymmetry and the Serotonergic Controls of Pre-Neural Morphogenesis

Levin¹,

2006

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Serotonin is a clinically important neurotransmitter regulating diverse aspects of cognitive function, sleep, mood, and appetite. Increasingly, it is becoming appreciated that serotonin signaling among non-neuronal cells is a novel patterning mechanism existing throughout diverse phyla. Here, we review the evidence implicating serotonergic signaling in embryonic morphogenesis, including gastrulation, craniofacial and bone patterning, and the generation of left-right asymmetry. We propose two models suggesting movement of neurotransmitter molecules as a novel mechanism for how bioelectrical events may couple to downstream signaling cascades and gene activation networks. The discovery of serotonin-dependent patterning events occurring long before the development of the nervous system opens exciting new avenues for future research in evolutionary, developmental, and clinical biology.

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Section: Serotonergic Regulation Of Mouse Craniofacial Developmentmentioning

confidence: 99%

Section: Serotonergic Regulation Of Mouse Craniofacial Developmentmentioning

confidence: 99%

Of Minds and Embryos: Left-Right Asymmetry and the Serotonergic Controls of Pre-Neural Morphogenesis

Levin¹,

2006

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“…In the mouse embryo, accumulated evidence suggests that circulating serotonin (5-hydroxytryptamine, 5-HT) regulates various aspects of craniofacial development, including cranial neural crest migration [Moiseiwitsch and Lauder, 1995], morphogenesis of tooth germs and other craniofacial structures, and expression of several 'morphoregulatory molecules' [Edelman and Jones, 1992], such as growth factors, cell adhesion and extracellular matrix molecules, by activation of appropriate 5-HT receptor subtypes [Shuey et al, 1992Yavarone et al, 1993;Launay et al, 1996;Lauder, 1995, 1997;Choi et al, 1997;Moiseiwitsch et al, 1998]. …”

Section: Introductionmentioning

confidence: 99%

Activation of 5-HT Receptors That Stimulate the Adenylyl Cyclase Pathway Positively Regulates IGF-I in Cultured Craniofacial Mesenchymal Cells

2001

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Results of the present study demonstrate that activation of the adenylyl cyclase/protein kinase A (PKA) pathway leads to increased levels of insulin-like growth factor I (IGF-I) in cultured embryonic mouse mandibular mesenchymal cells. Treatment of serum-free cultures with 10^–8M 8-OH-DPAT (DPAT) or with 10^–5M forskolin in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX; 10^–5M) increased levels of IGF-I (but not IGF-II), as measured by [¹²⁵I]protein A immunobinding. In a previous study, we showed that DPAT, forskolin, IBMX and the 5-HT₄ receptor agonist SC53116 all increased the synthesis of cyclic adenosine monophosphate (cAMP) in these cultures. Taken together, these results provide evidence that stimulation of the adenylyl cyclase/PKA pathway in embryonic mandibular mesenchymal cells positively regulates IGF-I. This is supported by the ability of the PKA inhibitor Rp-cAMPS to block increases in IGF-I caused by both DPAT and forskolin. Consistent with these results, DPAT and forskolin increased phosphorylation of the cAMP response element binding protein (CREB), which was also blocked by Rp-cAMPS. These results suggest that activation of 5-HT receptors positively coupled to the adenylyl cyclase/PKA pathway may promote transcription of IGF-I through a cAMP response element (CRE) in the IGF-I promoter. This may represent one mechanism whereby 5-HT positively regulates IGF-I expression in developing craniofacial mesenchymal cells.

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“…In the neurulating mouse embryo, recent studies have shown that 5-HT regulates various aspects of craniofacial development, including cranial neural crest migration, morphogenesis of tooth germs and other craniofacial structures [Shuey et al, 1992Choi et al, 1997], as well as expression of several 'morphoregulatory molecules' [Edelman and Jones, 1992] such as growth factors and cell adhesion and extracellular matrix molecules. These effects appear to be mediated by specific 5-HT receptor subtypes [Launay et al, 1996;Lauder, 1995, 1997;Moiseiwitsch et al, 1998]. …”

Section: Introductionmentioning

confidence: 99%

Serotonin Receptor Agonists That Increase Cyclic AMP Positively Regulate IGF-I in Mouse Mandibular Mesenchymal Cells

Lambert

Jm²

1999

Dev Neurosci

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Evidence from the present study suggests that activation of both 5-HT_1A and 5-HT₄ (5-hydroxytryptamine) receptor subtypes stimulates cyclic adenosine monophosphate (cAMP) synthesis in cultured embryonic mouse mandibular mesenchymal cells (micromass cultures). When these cells were grown in serum-free medium and treated with 10^–8 M agonist selective for either the 5-HT_1A or 5-HT₄ receptor subtype (8-OH-DPAT and SC53116, respectively), this significantly stimulated cAMP synthesis and increased insulin-like growth factor I (IGF-I), but not IGF-II, protein levels compared to vehicle-treated controls, as measured by semi-quantitative immunobinding assays. Consistent with these results, IGF-I was significantly decreased when mandibular mesenchymal cells were grown in serum-containing medium (which contains micromolar amounts of 5-HT from fetal calf serum) and treated with 10^–8 M antagonist selective for the 5-HT_1A or 5-HT₄ receptor subtype (NAN-190 on SDZ-205,557). Forskolin also stimulated cAMP and IGF-I (but not IGF-II) in both serum-containing and serum-free cultures. These results indicate that activation of 5-HT receptors that increase cAMP promotes synthesis of IGF-I. This may occur by activation of the cAMP response element sequence present in the IGF-I promoter region. Stimulation of the adenylyl cyclase pathway by activation of 5-HT_1A or 5-HT₄ receptors may be one mechanism by which serotonin regulates IGF-I synthesis in developing craniofacial mesenchymal cells.

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Regulation by serotonin of tooth-germ morphogenesis and gene expression in mouse mandibular explant cultures

Cited by 35 publications

References 28 publications

Of Minds and Embryos: Left-Right Asymmetry and the Serotonergic Controls of Pre-Neural Morphogenesis

Of Minds and Embryos: Left-Right Asymmetry and the Serotonergic Controls of Pre-Neural Morphogenesis

Activation of 5-HT Receptors That Stimulate the Adenylyl Cyclase Pathway Positively Regulates IGF-I in Cultured Craniofacial Mesenchymal Cells

Serotonin Receptor Agonists That Increase Cyclic AMP Positively Regulate IGF-I in Mouse Mandibular Mesenchymal Cells

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