Msx2 controls ameloblast terminal differentiation

Msx2 controls ameloblast terminal differentiation
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DOI:
10.1002/dvdy.20182
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发表时间:
2004-12-01
影响因子:
2.5
通讯作者:
Maas, R
Maas, R
中科院分区:
生物学3区
文献类型:
--
作者:
Bei, M;Stowell, S;Maas, R

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晚期牙齿形态发生的特征是一系列决定牙尖形态发生和上皮细胞组织分化为分泌釉质成釉细胞的事件。缺乏同源框基因 Msx2 的小鼠在牙尖形态发生和釉质形成过程中表现出缺陷。为了更好地了解 Msx2 突变牙齿缺陷的基础,我们研究了 Msx2 在牙齿形态发生后期的功能。牙尖的形成被认为是在牙釉质结的控制下,牙釉质结被认为在此过程中充当组织中心(Vaahtokari 等人 [1996] Mech. Dev. 54:39-43)。骨形态发生蛋白-4(BMP4)已被建议通过调节程序性细胞死亡来介导釉质结信号传导的终止(Jernvall等人[1998]Development 125-161-169)。在这里,我们表明牙釉质结中的 Bmp4 表达是 Msx2 依赖性的。我们进一步表明,在成釉细胞形成过程中,Msx2 是细胞外基质基因层粘连蛋白 5 α 3 表达所必需的,已知该基因在成釉细胞分化过程中发挥重要作用。因此,这一结果为理解转录因子和细胞外基质如何​​整合到控制细胞分化的发育途径中提供了范例。 (C) 2004 Wiley-Liss, Inc.
Late tooth morphogenesis is characterized by a series of events that determine cusp morphogenesis and the histodifferentiation of epithelial cells into enamel-secreting ameloblasts. Mice lacking the homeobox gene Msx2 exhibit defects in cusp morphogenesis and in the process of amelogenesis. To better understand the basis of the Msx2 mutant tooth defects, we have investigated the function of Msx2 during late stages of tooth morphogenesis. Cusp formation is thought to be under the control of the enamel knot, which has been proposed to act as an organizing center during this process (Vaahtokari et al. [1996] Mech. Dev. 54:39-43). Bone morphogenetic protein-4 (BMP4) has been suggested to mediate termination of enamel knot signaling by means of regulation of programmed cell death (Jernvall et al. [1998] Development 125-161-169). Here, we show that Bmp4 expression in the enamel knot is Msx2-dependent. We further show that during amelogenesis Msx2 is required for the expression of the extracellular matrix gene Laminin 5 alpha 3, which is known to play an essential role during ameloblast differentiation. This result thus provides a paradigm for understanding how transcription factors and extracellular matrix can be integrated into a developmental pathway controlling cell differentiation. (C) 2004 Wiley-Liss, Inc.