PI3K inhibition highlights new molecular interactions involved in the skeletogenesis of Paracentrotus lividus embryos.
Animals
Bone Development
/ drug effects
Bone and Bones
/ drug effects
Chromones
/ pharmacology
Computational Biology
Embryo, Nonmammalian
Epistasis, Genetic
/ drug effects
Gene Expression Profiling
Gene Expression Regulation, Developmental
/ drug effects
Gene Regulatory Networks
/ drug effects
Morpholines
/ pharmacology
Paracentrotus
/ drug effects
Phosphatidylinositol 3-Kinases
/ metabolism
Phosphoinositide-3 Kinase Inhibitors
/ pharmacology
Protein Binding
/ drug effects
Signal Transduction
/ drug effects
Growth factors
In silico analysis
Kinase
Primary mesenchyme cells
Spicule matrix proteins
Transcription factors
Journal
Biochimica et biophysica acta. Molecular cell research
ISSN: 1879-2596
Titre abrégé: Biochim Biophys Acta Mol Cell Res
Pays: Netherlands
ID NLM: 101731731
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
16
04
2019
revised:
05
09
2019
accepted:
10
09
2019
pubmed:
17
9
2019
medline:
21
4
2020
entrez:
17
9
2019
Statut:
ppublish
Résumé
The sea urchin embryo develops a well-defined biomineralized endoskeleton, synthesized exclusively by the skeletogenic cells, supported by ectodermal cues for the correct skeleton patterning. The biomineralization process is tightly regulated via a hierarchical order of gene expression, including transcription and growth factors, biomineralization proteins. Recently, the role of kinases and intracellular signaling pathways in sea urchin skeletogenesis has been addressed, although the downstream components still remain unknown. In this study, we investigated the role of phosphatidylinositide 3-kinase (PI3K)-mediated signaling pathway in Paracentrotus lividus, to identify its genes/proteins targets. The effects of LY294002 (LY), a PI3K-specific inhibitor, were evaluated at morphological and molecular levels. Treatment with 40 μM LY from the blastula stage completely blocked skeleton deposition, which was reversed by wash out experiments. Besides, LY caused a slight delay in the tripartite gut development. Despite the skeleton absence, a few skeleton-specific proteins/mRNAs were regularly expressed and localized in LY-treated embryos, as shown for MSP130 and SM50 by immunofluorescence and in situ hybridization experiments. QPCR analyses showed that LY differently affected the expression of genes coding for other biomineralization proteins, transcription and growth factors. SM30 and carbonic anhydrase expression was severely downregulated, while almost all the transcription factors analyzed were upregulated. Based on the present results and in silico analyses, we propose an "interactomic" model simulating PI3K connections in P. lividus embryos. Our findings define a novel regulatory step in the embryonic skeletogenesis, and provide valuable molecular data for further studies on the role of PI3K signaling in invertebrate biomineralization.
Identifiants
pubmed: 31525406
pii: S0167-4889(19)30169-7
doi: 10.1016/j.bbamcr.2019.118558
pii:
doi:
Substances chimiques
Chromones
0
Morpholines
0
Phosphoinositide-3 Kinase Inhibitors
0
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
31M2U1DVID
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
118558Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.