CaMK-II activation is essential for zebrafish inner ear development and acts through Delta-Notch signaling.
CaMK-II activation is essential for zebrafish inner ear development and acts through Delta-Notch signaling.
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CaMK-II 激活对于斑马鱼内耳发育至关重要，并通过 Delta-Notch 信号传导发挥作用。
DOI：
10.1016/j.ydbio.2013.05.028
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发表时间：
2013
影响因子：
2.7
通讯作者：
Tombes,RobertM
中科院分区：
文献类型：
--
作者：
Rothschild,SarahC;Lahvic,Jamie;Francescatto,Ludmila;McLeod,JamieJA;Burgess,ShawnM;Tombes,RobertM
斑马鱼内耳发育的特征是耳石结晶成从感觉“毛”细胞突起的静止的动丝。这些感觉结构的典型形成依赖于关键模式基因的表达和钙离子信号。内耳中钙信号的一个潜在靶点是II型钙/钙调蛋白依赖的蛋白激酶(CaMK-II)，它在毛细胞中优先激活，在动纤毛的底部强烈激活。在斑马鱼中，CaMK-II由七个基因编码；其中一个基因(Camk2g1)的表达在毛细胞中丰富。用反义吗啉寡核苷酸抑制camk2g1的表达或用药物拮抗剂KN-93抑制CaMK-II的激活会导致耳石的异常形成，而不会阻止纤毛的形成。事实上，抑制CaMK-II会导致额外的纤毛细胞和Delta-Notch信号成员的水平改变。在CaMK-II变形体的毛细胞中，DeltaA和DeltaD转录本增加，DeltaD蛋白积聚，表明有缺陷的循环和/或胞吐功能。我们的发现表明，CaMK-II在发育中的耳朵中起着关键作用，通过核外对Delta-Notch信号的影响来影响细胞分化。在老年胚胎中，CaMK-II在斑点和脊部持续表达和激活，提示其在听觉成熟和转导中继续发挥作用。
Zebrafish inner ear development is characterized by the crystallization of otoliths onto immotile kinocilia that protrude from sensory “hair” cells. The stereotypical formation of these sensory structures is dependent on the expression of key patterning genes and on Ca2+signals. One potential target of Ca2+signaling in the inner ear is the type II Ca2+/calmodulin-dependent protein kinase (CaMK-II), which is preferentially activated in hair cells, with intense activation at the base of kinocilia. In zebrafish, CaMK-II is encoded by seven genes; the expression of one of these genes (camk2g1) is enriched in hair cells. The suppression ofcamk2g1expression by antisense morpholino oligonucleotides or inhibition of CaMK-II activation by the pharmacological antagonist, KN-93, results in aberrant otolith formation without preventing cilia formation. In fact, CaMK-II suppression results in additional ciliated hair cells and altered levels of Delta–Notch signaling members. DeltaA and deltaD transcripts are increased and DeltaD protein accumulates in hair cells of CaMK-II morphants, indicative of defective recycling and/or exocytosis. Our findings indicate that CaMK-II plays a critical role in the developing ear, influencing cell differentiation through extranuclear effects on Delta–Notch signaling. Continued expression and activation of CaMK-II in maculae and cristae in older embryos suggests continued roles in auditory sensory maturation and transduction.
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影响因子：
7.5
作者：
Kandachar, Vasundhara;Roegiers, Fabrice
通讯作者：
Roegiers, Fabrice
DOI：
10.1007/978-94-007-2888-2_30
发表时间：
2012-01-01
期刊：
CALCIUM SIGNALING
影响因子：
--
作者：
Maier, Lars S.
通讯作者：
Maier, Lars S.
影响因子：
19
作者：
Czarnecki, Peter G.;Shah, Jagesh V.
通讯作者：
Shah, Jagesh V.
影响因子：
11.8
作者：
Itoh, M;Kim, CH;Chitnis, AB
通讯作者：
Chitnis, AB
DOI：
--
发表时间：
1995-09
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
--
作者：
Robert M. Tombes;Steven Grant;EH Westin;Geoffrey W. Krystal
通讯作者：
Robert M. Tombes;Steven Grant;EH Westin;Geoffrey W. Krystal