Transcriptomic Profiling of Ca$^{2+}$ Transport Systems during the Formation of the Cerebral Cortex in Mice

Alexandre Bouron (1, 2)

1 GenChem - Genetics and Chemogenomics
2 BGE - UMR S1038 - Laboratoire de Biologie à Grande Échelle

Cytosolic calcium (Ca$^{2+}$) transients control key neural processes, including neurogenesis, migration, the polarization and growth of neurons, and the establishment and maintenance of synaptic connections. They are thus involved in the development and formation of the neural system. In this study, a publicly available whole transcriptome sequencing (RNA-Seq) dataset was used to examine the expression of genes coding for putative plasma membrane and organellar Ca$^{2+}$-transporting proteins (channels, pumps, exchangers, and transporters) during the formation of the cerebral cortex in mice. Four ages were considered: embryonic days 11 (E11), 13 (E13), and 17 (E17), and post-natal day 1 (PN1). This transcriptomic profiling was also combined with live-cell Ca$^{2+}$ imaging recordings to assess the presence of functional Ca$^{2+}$ transport systems in E13 neurons. The most important Ca$^{2+}$ routes of the cortical wall at the onset of corticogenesis (E11-E13) were TACAN, GluK5, nAChR $\beta$2, Cav3.1, Orai3, transient receptor potential cation channel subfamily M member 7 (TRPM7) non-mitochondrial Na$^+$/Ca$^{2+}$ exchanger 2 (NCX2), and the connexins CX43/CX45/CX37. Hence, transient receptor potential cation channel mucolipin subfamily member 1 (TRPML1), transmembrane protein 165 (TMEM165), and Ca$^{2+}$ "leak" channels are prominent intracellular Ca$^{2+}$ pathways. The Ca$^{2+}$ pumps sarco/endoplasmic reticulum Ca$^{2+}$ ATPase 2 (SERCA2) and plasma membrane Ca$^{2+}$ ATPase 1 (PMCA1) control the resting basal Ca2+ levels. At the end of neurogenesis (E17 and onward), a more numerous and diverse population of Ca$^{2+}$ uptake systems was observed. In addition to the actors listed above, prominent Ca$^{2+}$-conducting systems of the cortical wall emerged, including acid-sensing ion channel 1 (ASIC1), Orai2, P2X2, and GluN1. Altogether, this study provides a detailed view of the pattern of expression of the main actors participating in the import, export, and release of Ca$^{2+}$. This work can serve as a framework for further functional and mechanistic studies on Ca$^{2+}$ signaling during cerebral cortex formation.

Mots clés: Na/Ca exchanger; calcium channels; calcium pumps; calcium stores; cerebral cortex; endoplasmic reticulum; neurogenesis

Domaines: Neurobiologie

Alexandre Bouron. Transcriptomic Profiling of Ca$^{2+}$ Transport Systems during the Formation of the Cerebral Cortex in Mice. Cells, 2020, 9 (8), pp.1800. ⟨10.3390/cells9081800⟩. ⟨hal-02925944⟩