Involvement of bone morphogenetic protein-4 and bone morphogenetic protein-7 in the differentiation of the adrenergic phenotype in developing sympathetic neurons

Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 2079-2088 ◽  
Author(s):  
E. Reissmann ◽  
U. Ernsberger ◽  
P.H. Francis-West ◽  
D. Rueger ◽  
P.M. Brickell ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Proteins ◽  
Sympathetic Neurons ◽  
Sympathetic Neuron ◽  
Dorsal Aorta ◽  
Bone Morphogenetic Protein 4 ◽  
Bone Morphogenetic Protein 7 ◽  
Neuron Differentiation ◽  
Embryonic Tissues ◽  
Morphogenetic Protein

The neurotransmitter phenotype of sympathetic neurons is specified by interactions with the surrounding embryonic tissues. Adrenergic differentiation is elicited early during development in the vicinity of notochord and dorsal aorta and the importance of axial midline tissues for adrenergic differentiation has been well documented. We now provide evidence that bone morphogenetic proteins, BMP-4 and BMP-7 are signals produced by the dorsal aorta that direct sympathetic neuron differentiation. BMP-4 and BMP-7 are expressed in the dorsal aorta at critical times during sympathetic neuron differentiation and have the ability to enhance the formation of adrenergic sympathetic neurons both in cultures of neural crest cells and when ectopically expressed in the developing embryo.

scholarly journals Association of distinct type 1 bone morphogenetic protein receptors with different molecular pathways and survival outcomes in neuroblastoma

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Amnah M. Alshangiti ◽  
Sean L. Wyatt ◽  
Erin McCarthy ◽  
Louise M. Collins ◽  
Shane V. Hegarty ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Proteins ◽  
Sympathetic Neurons ◽  
Distinct Type ◽  
Dominant Negative ◽  
Survival Outcomes ◽  
Mycn Amplification ◽  
Morphogenetic Protein ◽  
Stage 4 ◽  
Cultured Sympathetic Neurons

Abstract Neuroblastoma (NB) is a paediatric cancer that arises in the sympathetic nervous system. Patients with stage 4 tumours have poor outcomes and 20% of high-risk cases have MYCN amplification. The bone morphogenetic proteins (BMPs) play roles in sympathetic neuritogenesis, by signalling through bone morphogenetic protein receptor (BMPR)2 and either BMPR1A or BMPR1B. Alterations in BMPR2 expression have been reported in NB; it is unknown if the expression of BMPR1A or BMPR1B is altered. We report lower BMPR2 and BMPR1B, and higher BMPR1A, expression in stage 4 and in MYCN-amplified NB. Kaplan–Meier plots showed that high BMPR2 or BMPR1B expression was linked to better survival, while high BMPR1A was linked to worse survival. Gene ontology enrichment and pathway analyses revealed that BMPR2 and BMPR1B co-expressed genes were enriched in those associated with NB differentiation. BMPR1A co-expressed genes were enriched in those associated with cell proliferation. Moreover, the correlation between BMPR2 and BMPR1A was strengthened, while the correlation between BMPR2 and BMPR1B was lost, in MYCN-amplified NB. This suggested that differentiation should decrease BMPR1A and increase BMPR1B expression. In agreement, nerve growth factor treatment of cultured sympathetic neurons decreased Bmpr1a expression and increased Bmpr1b expression. Overexpression of dominant negative BMPR1B, treatment with a BMPR1B inhibitor and treatment with GDF5, which signals via BMPR1B, showed that BMPR1B signalling is required for optimal neuritogenesis in NB cells, suggesting that loss of BMPR1B may alter neuritogenesis. The present study shows that expression of distinct BMPRs is associated with different survival outcomes in NB.

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