Restricted expression of a novel murine atonal-related bHLH protein in undifferentiated neural precursors

Restricted expression of a novel murine atonal-related bHLH protein in undifferentiated neural precursors
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DOI:
10.1006/dbio.1996.0297
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发表时间:
1996-11-25
影响因子:
2.7
通讯作者:
Guillemot, F
Guillemot, F
中科院分区:
生物学3区
文献类型:
--
作者:
Gradwohl, G;Fode, C;Guillemot, F

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组织特异性bHLH蛋白在无脊椎动物和脊椎动物神经细胞谱系的特化和分化中起重要作用。两组bHLH蛋白质,无调和achaete-scute,在果蝇中具有前神经活性,并且小鼠achaete-scute同源物MASH 1是几种神经谱系分化所需的。在筛选与MASH 1相互作用的蛋白质时,我们分离出一种与无调相关的新型bHLH蛋白,命名为MATH 4A,它广泛表达于小鼠胚胎CNS和PNS的神经前体细胞中。在酵母和体外的相互作用试验表明,MATH 4A有效地与MASH 1和无处不在的bHLH蛋白E12相互作用。MATH 4A-E12异二聚体,而不是MATH 4A-MASH 1,结合共有的E盒序列。Math 4A的表达仅限于未分化的神经前体,并且在神经系统的大多数区域中与Mash 1的表达互补。特别地,Math 4A在大脑皮层、背侧丘脑和上鳃中以高水平转录。基板,其呈现很少或没有Mash 1表达。然而,这两种基因的表达在某些CNS区域(视网膜、下丘脑的视前区、中脑、后脑)中显示出有限的重叠。它的结构和表达模式表明,MATH 4A可以调节神经发育的早期步骤,无论是作为无处不在的bHLH蛋白的伴侣或与其他神经特异性bHLH蛋白相关。(C)出版社:Academic Press,Inc.
Tissue-specific bHLH proteins play important roles in the specification and differentiation of neural cell lineages in invertebrate and vertebrate organisms. Two groups of bHLH proteins, atonal and achaete-scute, have proneural activities in Drosophila, and the mouse achaete-scute homolog MASH1 is required for the differentiation of several neural lineages. In a screen for proteins interacting with MASH1, we have isolated a novel bHLH protein related to atonal, named MATH4A, which is broadly expressed in neural precursor cells in the mouse embryonic CNS and PNS. Interaction assays in yeast and in vitro demonstrate that MATH4A interacts efficiently with both MASH1 and the ubiquitous bHLH protein E12. MATH4A-E12 heterodimers, but not MATH4A-MASH1, bind to a consensus E-box sequence. Math4A expression is restricted to undifferentiated neural precursors and is complementary to that of Mash1 in most regions of the nervous system. In particular, Math4A is transcribed at high levels in the cerebral cortex, dorsal thalamus, and epibranchial. placodes, which present little or no Mash1 expression. However, expression of the two genes shows limited overlap in certain CNS regions (retina, preoptic area of the hypothalamus, midbrain, hindbrain). Its structure and expression pattern suggest that MATH4A may regulate an early step of neural development, either as a partner of ubiquitous bHLH proteins or associated with other neural-specific bHLH proteins. (C) 1996 Academic Press, Inc.