P57Kip2 expression is enhanced during mid-cardiac murine development and is restricted to trabecular myocardium
P57Kip2 expression is enhanced during mid-cardiac murine development and is restricted to trabecular myocardium
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DOI：
10.1203/00006450-199905010-00004
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发表时间：
1999-05-01
影响因子：
3.6
通讯作者：
Epstein, JA
中科院分区：
文献类型：
--
作者：
Kochilas, LK;Li, J;Epstein, JA
在胚胎发育过程中，心脏需要在大小和细胞数量上增长，经历复杂的形态改变，并发挥血液循环的功能。在胚胎10.5 d （E10.5）至E11.5之间，心肌细胞快速分裂，导致心脏质量增加一倍，同时代谢需求增加，收缩力增强。心肌细胞分化的加速伴随着心室心肌小梁的显著增加。小鼠的许多单基因突变导致“心肌变薄”和E10.5和E13.5之间继发于心力衰竭的胚胎死亡率。这就是斑点小鼠Pax3基因突变导致神经嵴和心脏缺陷的情况。然而，控制这些重要发育步骤的分子事件在很大程度上仍然未知。在这里，我们描述了使用抑制减法杂交来鉴定mRNA转录本，其表达在正常心脏的这一关键时期增强。这些基因编码与收缩器官成熟、心肌细胞分化、细胞代谢改变和转录调控相关的功能。我们发现的其中一个基因p57（Kip2）编码p21家族的周期蛋白依赖性激酶抑制剂。我们发现p57（Kip2）通常在发育中的心脏的内小梁层表达。在斑点胚胎中，p57（Kip2）的表达扩展到覆盖整个心肌厚度。这一结果和进一步的结构分析表明，斑点胚胎的心肌缺陷与心肌细胞过早分化有关。
During embryonic development the heart is required to grow in size and cell number, undergo complex morphologic alterations, and function to circulate the blood. Between embryonic d 10.5 (E10.5) and E11.5, cardiac myocytes undergo rapid cell division, resulting in doubling of cardiac mass, while metabolic requirements are increased and contraction force is enhanced. Accelerated cardiomyocyte differentiation is accompanied by a significant increase in trabeculation of ventricular myocardium. Many single gene mutations in the mouse result in a "thinned myocardium" and embryonic lethality between E10.5 and E13.5 secondary to heart failure. This is the case in the Splotch mouse in which a mutation of the Pax3 gene results in neural crest and cardiac defects. Nevertheless, the molecular events governing these important developmental steps remain largely unknown. Here, we describe the use of suppression subtractive hybridization to identify mRNA transcripts whose expression is enhanced during this critical period in normal hearts. These genes encode functions related to maturation of the contractile apparatus, cardiomyocyte differentiation, altered cellular metabolism, and transcriptional regulation. One of the genes that we identified, p57(Kip2), encodes a cyclin-dependent kinase inhibitor of the p21 family. We show that p57(Kip2) is normally expressed in the inner trabecular layer of the developing heart. In Splotch embryos, expression of p57(Kip2) is expanded to encompass the entire thickness of the myocardium. This result and further structural analysis suggests that the myocardial defect of Splotch embryos is associated with precocious cardiomyocyte differentiation.