Non-cell autonomous and non-catalytic activities of ATX in the developing brain

Greenman, Raanan; Gorelik, Anna; Sapir, Tamar; Baumgart, Jan; Zamor, Vanessa; Segal-Salto, Michal; Levin-Zaidman, Smadar; Aidinis, Vassilis; Aoki, Junken; Nitsch, Robert; Vogt, Johannes; Reiner, Orly

doi:10.3389/fnins.2015.00053

Cited by 22 publications

(20 citation statements)

References 91 publications

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“…The multiple correlations found in our study between ATX and other bioactive compounds such as BDNF, FGF21, leptin and adiponectin besides the lack of correlation between ATX and LPA in human milk, strengthen the idea that the role of ATX in neuronal development is predominantly catalytic-independent [20] . Meanwhile GDNF and GFAP levels decreased from colostrum to mature milk and their correlation with ATX is stronger as the lactation goes on.…”

Section: Discussionsupporting

confidence: 80%

Bioactive Components in Human Milk Along the First Month of Life: Effects of Iodine Supplementation during Pregnancy

et al. 2016

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Background/Aims: Human milk is considered the most suitable food for infants. The potential benefits of breastfeeding can be explained by the presence of different growth and neurotrophic factors in human milk. This study was designed to detect some biomarkers in human milk, which could be involved in the infant neurodevelopment and in the regulation of the maturation of neonatal intestine (brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), fibroblast growth factor 21 (FGF21), lysophosphatidic acid (LPA) and autotaxin (ATX)), and compare them on the basis of the consumption of iodine supplements or multivitamins. Methods: A prospective study included 37 healthy breastfeeding mothers, divided into 3 different groups: (1) 10 mothers who did not take supplements, (2) 17 mothers who took potassium iodine (KI) 200 µg/day and (3) 10 mothers who took a multivitamin supplement. Results: The concentrations of BDNF, GDNF, GFAP, FGF21, LPA and ATX in human milk were not significantly different in women who took a multivitamin or KI supplement compared with those who did not take any supplement. Conclusions: The presence of neurotrophic factors in human milk is neither modified by the consumption of supplements nor by their type.

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Section: Discussionsupporting

confidence: 80%

Bioactive Components in Human Milk Along the First Month of Life: Effects of Iodine Supplementation during Pregnancy

et al. 2016

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“…LysoPLD/ATX encodes one of the major enzymes involved in synthesis of lysophospatidic acid (LPA), a molecule with a key signaling role controlling both excitatory and inhibitory synapse functions (García-Morales et al., 2015, Vogt et al., 2015). LPA has a critical role in the nervous system: knockout of LPA1 receptor causes anxiety (Santin et al., 2009), which also characterizes the Slm2 mouse, and LysoPLD/ATX is essential for brain development (Greenman et al., 2015). An LPA1-deficient mouse was also observed to display reductions in γ oscillations, albeit in the entorhinal cortex and not the hippocampus (Cunningham et al., 2006).…”

Section: Discussionmentioning

confidence: 99%

A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

et al. 2016

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SummaryThe brain is made up of trillions of synaptic connections that together form neural networks needed for normal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins, including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neural network activity is unknown. Here, we find that SLM2 levels are maintained by a homeostatic feedback control pathway that predates the divergence of SLM2 and Sam68. SLM2 also controls the splicing of Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, and Cask, each of which are important for synapse function. Cortical neural network activity dependent on synaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased in Slm2-null mice. Additionally, these mice are anxious and have a decreased ability to recognize novel objects. Our data reveal a pathway of SLM2 homeostatic auto-regulation controlling brain network activity and behavior.

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“…While genetic loss of function can reveal cell-autonomous gene functions, the contribution of non-cell-autonomous gene functions and/or community effects often remain poorly defined. Non-cell-autonomous gene functions may involve directed cell-to-cell communication either via contact-mediated or secreted signaling cues (Greenman et al, 2015;Hippenmeyer, 2014). For instance, excess activation of AKT3 in just a small population of cells is associated with human focal malformations (legend continued on next page) in cortical development, which disrupts the architecture of the entire hemisphere (Baek et al, 2015).…”

Section: Genetic Dissection Of Cell-autonomous Gene Function and Envimentioning

confidence: 99%

“…Such a phenomenon is also observed in distinct cellular contexts including collective cell migration and tissue morphogenesis (Heisenberg and Bellaïche, 2013). The cellular and molecular mechanisms orchestrating community effects during brain development are mostly unknown due to the lack of experimental assays enabling the visualization and quantitative assessment of the non-cell-autonomous elements in full or whole tissue conditional loss-of-function phenotypic analysis (Greenman et al, 2015). To this end, we have established an unprecedented genetic strategy to visualize and dissect the interplay of relative cell-autonomous gene function and the contribution of non-cell-autonomous community effects to the overall phenotype presentation.…”

Section: Genetic Dissection Of Cell-autonomous Gene Function and Envimentioning

confidence: 99%

Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells

Beattie

Postiglione

Burnett

et al. 2017

Neuron

104

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The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.

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Non-cell autonomous and non-catalytic activities of ATX in the developing brain

Cited by 22 publications

References 91 publications

Bioactive Components in Human Milk Along the First Month of Life: Effects of Iodine Supplementation during Pregnancy

Bioactive Components in Human Milk Along the First Month of Life: Effects of Iodine Supplementation during Pregnancy

A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells

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