Distinct domains within Mash1 and Math1 are required for function in neuronal differentiation versus neuronal cell-type specification
Distinct domains within Mash1 and Math1 are required for function in neuronal differentiation versus neuronal cell-type specification
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DOI：
10.1242/dev.01008
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发表时间：
2004-03-01
期刊：
影响因子：
4.6
通讯作者：
Johnson, JE
中科院分区：
文献类型：
--
作者：
Nakada, Y;Hunsaker, TL;Johnson, JE
碱性螺旋-环-螺旋（bHLH）转录因子家族的许多成员在多种组织和生物体的发育中起关键作用。我们确定活动的神经bHLH蛋白Mash 1和Math 1在诱导神经元分化，并在诱导形成不同的背中间神经元亚型在鸡神经管。虽然这两种因子诱导神经元分化，但每种因子在形成的背侧中间神经元类型中具有不同的活性，Math 1的过表达增加dI 1中间神经元，Mash 1增加dI 3中间神经元。Math 1和Mash 1作为这两种功能的转录激活因子发挥作用。此外，我们定义的bHLH基序，这些不同的活动所需的神经发育中的离散域。Mash 1 HLH结构域的HSP 1是Mash 1能够促进神经元分化所必需的，并且足以将这种活性赋予非神经bHLH因子MyoD。相反，Math 1的螺旋2以及Mash 1的螺旋1和2是这些因子的神经元特异性活动所需的结构域。Mash 1和Math 1的HLH基序内的不同结构域驱动神经元分化和细胞类型的规范的要求可能反映了这些功能中涉及的独特的蛋白质-蛋白质相互作用的重要性。
Many members of the basic helix-loop-helix (bHLH) family of transcription factors play pivotal roles in the development of a variety of tissues and organisms. We identify activities for the neural bHLH proteins Mash1 and Math1 in inducing neuronal differentiation, and in inducing the formation of distinct dorsal interneuron subtypes in the chick neural tube. Although both factors induce neuronal differentiation, each factor has a distinct activity in the type of dorsal interneuron that forms, with overexpression of Math1 increasing dI1 interneurons, and Mash1 increasing dI3 interneurons. Math1 and Mash1 function as transcriptional activators for both of these functions. Furthermore, we define discrete domains within the bHLH motif that are required for these different activities in neural development. Helix 1 of the Mash1 HLH domain is necessary for Mash1 to be able to promote neuronal differentiation, and is sufficient to confer this activity to the non-neural bHLH factor MyoD. In contrast, helix 2 of Math1, and both helix 1 and 2 of Mash1, are the domains required for the neuronal specification activities of these factors. The requirement for distinct domains within the HLH motif of Mash1 and Math1 for driving neuronal differentiation and cell-type specification probably reflects the importance of unique protein-protein interactions involved in these functions.