Non-cell autonomous and non-catalytic activities of ATX in the developing brain
The intricate formation of the cerebral cortex requires a well-coordinated series of events, which are regulated at the level of cell-autonomous and non-cell autonomous mechanisms. Whereas cell-autonomous mechanisms that regulate cortical development are well-studied, the non cell-autonomous mechanisms remain poorly understood. A non-biased screen allowed us to identify Autotaxin (ATX) as a non cell-autonomous regulator of neural stem cell proliferation. ATX (also known as ENPP2) is best known to catalyze lysophosphatidic acid (LPA) production. Our results demonstrate that ATX affects the localization and adhesion of neuronal progenitors in a cell autonomous and non-cell autonomous manner, …
Synaptic Phospholipid Signaling Modulates Axon Outgrowth via Glutamate-dependent Ca2+-mediated Molecular Pathways.
Abstract Altered synaptic bioactive lipid signaling has been recently shown to augment neuronal excitation in the hippocampus of adult animals by activation of presynaptic LPA2-receptors leading to increased presynaptic glutamate release. Here, we show that this results in higher postsynaptic Ca2+ levels and in premature onset of spontaneous neuronal activity in the developing entorhinal cortex. Interestingly, increased synchronized neuronal activity led to reduced axon growth velocity of entorhinal neurons which project via the perforant path to the hippocampus. This was due to Ca2+-dependent molecular signaling to the axon affecting stabilization of the actin cytoskeleton. The spontaneous…
LPA1, LPA2, LPA4, and LPA6receptor expression during mouse brain development
Background:LPA is a small bioactive phospholipid that acts as an extracellularsignaling molecule and is involved in cellular processes, including cell prolifera-tion, migration, and differentiation. LPA acts by binding and activating at least sixknown G protein–coupled receptors: LPA1–6. In recent years, LPA has beensuggested to play an important role both in normal neuronal development andunder pathological conditions in the nervous system. Results:We show the expression pattern of LPA receptors during mouse braindevelopment by using qRT-PCR, in situ hybridization, and immunocytochemistry.Only LPA1,LPA2,LPA4,and LPA6 mRNA transcripts were detected throughoutdevelopment stages from embryoni…