Expression and developmental regulation of gap junction connexins cx26, cx32, cx43 and cx45 in the rat midbrain-floor

Expression and developmental regulation of gap junction connexins cx26, cx32, cx43 and cx45 in the rat midbrain-floor
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DOI:
10.1016/s0736-5748(01)00056-9
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发表时间:
2002-02-01
影响因子:
1.8
通讯作者:
Reuss, B
Reuss, B
中科院分区:
医学4区
文献类型:
--
作者:
Leung, DSY;Unsicker, K;Reuss, B

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连接蛋白(cx)是一个跨膜蛋白家族,它能形成间隙连接通道,使细胞网络的代谢和电偶联得以进行。对cx在发育脑中表达的初步研究表明,ex可能经历动态变化,并可能与神经前体细胞和年轻神经元的同步发育和分化有关。我们研究了cx 26,cx 32,cx43和cx45在中脑底的表达,黑质纹状体多巴胺能神经元的起源和分化。这种神经元群体在调节运动功能方面具有重要意义。半定量逆转录酶-聚合酶链反应(RT-PCR)显示低水平的cx 26-mRNA在中脑底在E 12,在出生前和出生后的发展过程中逐渐增加,达到最大值在成人。Cx 32-mRNA水平在E16达到第一个峰值。并且在成年期表现出最高水平。Cx43在E12高度表达,直到E18降低,随后再次增加,直到成年。Cx45 mRNA在所有发育年龄均显著表达。但在产后第一周后略有下降。双标记的多巴胺能神经元标记酪氨酸羟化酶(TH),和CX-免疫反应(IR)的定量共聚焦激光显微镜评价显示不同的和相似的发展模式为个人CX调查。Cx 26在E14时最高。出生时下降,随后再次增加,达到成人E14水平的约50%。Cx 32-ir在E16达到高峰,出生后降至低水平。Cx43-ir在E12时最高。在E14时急剧下降。在出生时达到最低水平,但之后又略有增加。Cx45-ir显示双相模式,在E12和E18具有两个突出峰。随后是产后的大幅度下降。加在一起。结果表明,在中脑底和多巴胺能神经元中,cx的表达和免疫反应。分别遵循时间上与中脑形态发生的重要步骤一致的Cx型特异性模式,例如祖细胞形成和迁移(E12)。黑质纹状体系统的早期分化(E14-16)、目标相遇(E16-18)和出生后功能成熟。(C)2002年ISDN。由Elsevier Science B. V.出版,版权所有。
Connexins (cx) constitute a family of transmembrane proteins that form gap junction channels allowing metabolic and electrical coupling of cellular networks. Initial studies on the expression of cx in the developing brain have suggested that ex may undergo dynamic changes and may possibly be implicated in synchronizing development and differentiation of neural progenitor cells and young neurons. We have investigated expression of cx26, cx32, cx43, and cx45 in the midbrain floor, where nigrostriatal dopaminergic neurons originate and differentiate. This neuron population is of major importance in regulating motor-functions. Semiquantitative reverse transciptase-polymerase chain reaction (RT-PCR) revealed low levels of cx26-mRNA in the midbrain floor at E 12, which gradually increased during pre- and postnatal development, reaching a maximum in the adult. Cx32-mRNA-levels reached a first peak at E16. and showed highest levels in adulthood. Cx43 was highly expressed at E12, decreased until E 18, and subsequently increased again until adulthood. Cx45 mRNA was prominent at all developmental ages. but slightly decreased after the first postnatal week. Double-labeling for the dopaminergic neuronal marker tyrosine hydroxylase (TH), and cx-immunoreactivities (ir) evaluated by quantitative confocal laser microscopy revealed both distinct and similar developmental patterns for the individual cx investigated. Cx26 was highest at E14. decreased towards birth, and subsequently increased again reaching about 50% of the E 14 level in the adult. Cx32-ir peaked at E 16 and dropped to low levels after birth. Cx43-ir was highest at E12. decreased sharply at E14. reached its lowest levels at birth, but modestly increased again afterwards. Cx45-ir showed a biphasic pattern, with two prominent peaks at E 12 and E18. followed by a massive postnatal decrease. Taken together. our results reveal that expression and ir of cx in the midbrain floor and dopaminergic neurons. respectively, follow cx-type specific patterns that temporally coincide with important steps of midbrain morphogenesis, as e.g. progenitor cell formation and migration (E 12). early differentiation (E14-16), target encounter (E16-18) and postnatal functional maturation of the nigrostriatal system. (C) 2002 ISDN. Published by Elsevier Science B.V. All rights reserved.