Inductive specification and axonal orientation of spinal neurons mediated by divergent bone morphogenetic protein signaling pathways.
Inductive specification and axonal orientation of spinal neurons mediated by divergent bone morphogenetic protein signaling pathways.
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DOI：
10.1186/1749-8104-6-36
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发表时间：
2011-11-15
影响因子：
3.6
通讯作者：
Dodd J
中科院分区：
文献类型：
--
作者：
Perron JC;Dodd J
骨形态发生蛋白（BMP）7在发育中的脊髓背间神经元（dI神经元）中引起诱导和轴突定向反应。这些事件在脊髓神经元的发育过程中依次发生，但在这些和其他细胞类型中，如诱导和急性趋化反应同时发生，突出了细胞内信号传导的分化需求。I型和II型BMP受体亚型都有选择性地参与定向反应，但尚不清楚在给定的细胞中，分化是如何发生的。我们研究了背脊髓神经元中不同的BMP7活动产生的机制。我们发现，不同阈值浓度的BMP7需要引起不同的诱导和轴突定向反应。I型BMP受体激酶活性是激活pSmad信号和BMP7诱导dI特性所必需的，BMP7是一种高阈值反应。相比之下，I型BMP受体激酶活性和Smad1/5/8磷酸化都不参与dI轴突对BMP7的低阈值定向反应。相反，bmp7引起的轴突排斥和生长锥塌陷依赖于磷酸肌醇激酶（PI3K）的激活，可能通过II型受体信号传导。BMP7刺激dI神经元中pi3k依赖性信号。BMP6可引起神经诱导，但不具有定向活性，可激活Smad信号，但不刺激PI3K。通过psmad依赖和pi3k依赖（smad独立）机制的分化信号介导dI神经元对BMP7的诱导和定向反应。提出了一种模型，即BMP受体亚单位的选择性参与是信号通路选择的基础。
Bone morphogenetic protein (BMP)7 evokes both inductive and axon orienting responses in dorsal interneurons (dI neurons) in the developing spinal cord. These events occur sequentially during the development of spinal neurons but in these and other cell types such inductive and acute chemotactic responses occur concurrently, highlighting the requirement for divergent intracellular signaling. Both type I and type II BMP receptor subtypes have been implicated selectively in orienting responses but it remains unclear how, in a given cell, divergence occurs. We have examined the mechanisms by which disparate BMP7 activities are generated in dorsal spinal neurons. We show that widely different threshold concentrations of BMP7 are required to elicit the divergent inductive and axon orienting responses. Type I BMP receptor kinase activity is required for activation of pSmad signaling and induction of dI character by BMP7, a high threshold response. In contrast, neither type I BMP receptor kinase activity nor Smad1/5/8 phosphorylation is involved in the low threshold orienting responses of dI axons to BMP7. Instead, BMP7-evoked axonal repulsion and growth cone collapse are dependent on phosphoinositide-3-kinase (PI3K) activation, plausibly through type II receptor signaling. BMP7 stimulates PI3K-dependent signaling in dI neurons. BMP6, which evokes neural induction but does not have orienting activity, activates Smad signaling but does not stimulate PI3K. Divergent signaling through pSmad-dependent and PI3K-dependent (Smad-independent) mechanisms mediates the inductive and orienting responses of dI neurons to BMP7. A model is proposed whereby selective engagement of BMP receptor subunits underlies choice of signaling pathway.
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影响因子：
5.4
作者：
Heinecke K;Seher A;Schmitz W;Mueller TD;Sebald W;Nickel J
通讯作者：
Nickel J
DOI：
10.1083/jcb.109.4.1621
发表时间：
1989-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goslin K;Birgbauer E;Banker G;Solomon F
通讯作者：
Solomon F
影响因子：
2.7
作者：
Liu, J;Wilson, S;Reh, T
通讯作者：
Reh, T
影响因子：
16.2
作者：
DODD, J;MORTON, SB;JESSELL, TM
通讯作者：
JESSELL, TM
影响因子：
11.4
作者：
Lee-Hoeflich, ST;Causing, CG;Attisano, L
通讯作者：
Attisano, L