PMID- 23747599 OWN - NLM STAT- MEDLINE DCOM- 20131028 LR - 20130812 IS - 1095-564X (Electronic) IS - 0012-1606 (Linking) VI - 381 IP - 1 DP - 2013 Sep 1 TI - CaMK-II activation is essential for zebrafish inner ear development and acts through Delta-Notch signaling. PG - 179-88 LID - S0012-1606(13)00310-2 [pii] LID - 10.1016/j.ydbio.2013.05.028 [doi] AB - 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 of camk2g1 expression 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. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Rothschild, Sarah C AU - Rothschild SC AD - Department of Biology, Virginia Commonwealth University, Richmond, VA, USA. FAU - Lahvic, Jamie AU - Lahvic J FAU - Francescatto, Ludmila AU - Francescatto L FAU - McLeod, Jamie J A AU - McLeod JJ FAU - Burgess, Shawn M AU - Burgess SM FAU - Tombes, Robert M AU - Tombes RM LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20130607 PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Oligonucleotides) RN - 0 (Receptors, Notch) RN - 0 (delta protein) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) SB - IM MH - Animals MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism MH - Cilia/metabolism MH - Ear, Inner/*embryology MH - Enzyme Activation MH - Exocytosis MH - *Gene Expression Regulation, Developmental MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Membrane Proteins/*metabolism MH - Oligonucleotides/metabolism MH - Phosphorylation MH - Receptors, Notch/*metabolism MH - Signal Transduction MH - Zebrafish/*embryology OTO - NOTNLM OT - CaMK-II OT - Cilia OT - Delta-notch OT - Inner ear OT - Otolith EDAT- 2013/06/12 06:00 MHDA- 2013/10/29 06:00 CRDT- 2013/06/11 06:00 PHST- 2013/02/17 00:00 [received] PHST- 2013/05/28 00:00 [revised] PHST- 2013/05/29 00:00 [accepted] PHST- 2013/06/11 06:00 [entrez] PHST- 2013/06/12 06:00 [pubmed] PHST- 2013/10/29 06:00 [medline] AID - S0012-1606(13)00310-2 [pii] AID - 10.1016/j.ydbio.2013.05.028 [doi] PST - ppublish SO - Dev Biol. 2013 Sep 1;381(1):179-88. doi: 10.1016/j.ydbio.2013.05.028. Epub 2013 Jun 7.