Bone morphogenetic proteins in the nervous system

Mehler, Mark F.; Mabie, Peter C.; Zhang, Damin; Kessler, John A.

doi:10.1016/s0166-2236(96)01046-6

Cited by 376 publications

(280 citation statements)

References 65 publications

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“…Our data showing that the BMPs can promote both neuronal and astroglial cell differentiation are consistent with previous studies demonstrating that BMPs play multiple roles in development (Mehler et al, 1997). Other studies have found that the effects of BMPs can be age and tissue dependent (Grinspan et al, 2000;Mehler et al, 2000).…”

Section: Discussionsupporting

confidence: 93%

Signaling by Bone Morphogenetic Proteins and Smad1 Modulates the Postnatal Differentiation of Cerebellar Cells

Angley¹,

Kumar²,

Dinsio

et al. 2003

J. Neurosci.

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Previous studies have demonstrated that bone morphogenetic proteins (BMPs) activate the Smad1 signaling pathway to regulate cell determination and differentiation in the embryonic nervous system. Studies examining gene and protein expression in the rat cerebellum suggest that this pathway also regulates postnatal differentiation. Using microarrays, we found that Smad1 mRNA expression in the cerebellum increases transiently at postnatal day 6 (P6). Immunohistochemistry and Western blots showed that Smad1 and BMP4 proteins are present in the cerebellum, and that their expression also changes postnatally. The proteins are detectable at P4 -P6, a stage at which most cerebellar cells reside in the external germinal layer (EGL), where they extensively differentiate. The levels become maximal at P8 -P10, when neurons begin to migrate from the EGL into their mature positions in the internal granule layer. In cerebellar cultures prepared at P6 or P10, BMP4 activates Smad1 signaling to modulate cell differentiation. Brief BMP4 application caused Smad1 translocation from the neuronal cytoplasm into the nucleus, where it is known to regulate transcription in association with Smad4. Longer BMP4 treatment promoted the differentiation of both neuronal and non-neuronal cells. By 3 d, neuronal processes appeared more fasciculated, and the level of synaptotagmin, a protein found in synaptic vesicles, increased. In addition, many astroglial cells became more branched and stellate in morphology. The BMP-induced changes were reduced by treatment with antisense oligonucleotides to Smad1 or Smad4. These findings in vivo and in culture suggest that BMP4 and Smad1 signaling participate in regulating postnatal cerebellar differentiation.

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Section: Discussionsupporting

confidence: 93%

Signaling by Bone Morphogenetic Proteins and Smad1 Modulates the Postnatal Differentiation of Cerebellar Cells

Angley¹,

Kumar²,

Dinsio

et al. 2003

J. Neurosci.

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“…This is evident in the greater number of GABAergic interneurons that are derived from progenitor cells in the dorsolateral versus the dorsomedial wall of the telencephalon, where BMP expression is highest (Furuta et al 1997;Mehler et al 1997;Grove et al 1998). Exogenous Shh expression in the dorsomedial wall enhances the number of GABAergic interneurons (Gulacsi and Lillien 2003), whereas BMP signaling determines the fate of GABAergic interneuron pre-cursors, promoting differentiation of parvalbumin-positive interneurons and blocking differentiation of calbindin-and somatostatinpositive interneurons (Samanta et al 2007;Mukhopadhyay et al 2009).…”

Section: Forebrainmentioning

confidence: 99%

“…During late embryonic and postnatal periods, BMP signaling strongly induces astrocyte differentiation (Gross et al 1996;Mehler et al 1997;Fukuda et al 2007;See et al 2007). In culture, BMP signaling promotes astrogliogenesis in SVZ progenitor cells, cortical progenitor cells, and oligodendrocyte precursor cells (Gross et al 1996;Mabie et al 1999;Grinspan et al 2000).…”

Section: Astrocytesmentioning

confidence: 99%

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

Meyers

Kessler

2017

Cold Spring Harb Perspect Biol

128

107

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“…Today, more than 30 members of the BMP superfamily have been identified in various tissues and species, and it is known that they control a broad range of biological activities in many cell types like epithelial, mesenchymal or neuronal cells (Mehler et al, 1997;Turgeman et al, 2001). BMPs affect cellular processes like proliferation, differentiation, chemotaxis, motility or cell death (Hogan, 1996).…”

Section: Introductionmentioning

confidence: 99%

Functional implication of BMP4 expression on angiogenesis in malignant melanoma

et al. 2006

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Analyses of malignant melanomas revealed a strong expression of bone morphogenic proteins (BMPs) and their autocrine effect in promoting cell invasion and migration. Here, we report a paracrine effect of BMPs on the vascular network. Both BMP2 and BMP4 induced tube formation as well as the migratory efficiency of microvascular endothelial cells. Melanoma cells with reduced BMP activity attracted less endothelial cells in invasion assays than control cells. Furthermore, reduction of BMPs in melanoma cells had a strong effect on vasculogenic mimicry. Tube formation on matrigel was analysed for melanoma cells as well as in co-cultures of endothelial and melanoma cells. Melanoma cells with reduced BMP activity were not capable of forming cordlike structures by themselves and additionally inhibited tube formation of the endothelial cells. Genes involved in angiogenesis turned out to be strongly downregulated in these cell clones. Tumors derived from cells with impaired BMP activity showed reduced tumor growth or large necrotic areas owing to lack of angiogenesis in in vivo analyses.

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Bone morphogenetic proteins in the nervous system

Cited by 376 publications

References 65 publications

Signaling by Bone Morphogenetic Proteins and Smad1 Modulates the Postnatal Differentiation of Cerebellar Cells

Signaling by Bone Morphogenetic Proteins and Smad1 Modulates the Postnatal Differentiation of Cerebellar Cells

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

Functional implication of BMP4 expression on angiogenesis in malignant melanoma

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