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Lysophosphatidic Acid (LPA) Signaling in Neurogenesis

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Lipidomics of Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

LPA is a bioactive phospholipid with a plethora of roles in the developing and adult nervous system. LPA signaling mediates many processes in the brain including survival, development and function of neural progenitor cells, astrocytes, oligodendrocytes, and microglia. The intricate spatiotemporal pattern of LPA metabolism and receptor expression are critical for normal CNS development; altered LPA signaling underlies fetal lethality, neurodevelopmental deficits, and is associated with neuropsychiatric impairments and cognitive decline. Fetal hypoxic and hemorrhagic injuries are major causes for neurodevelopmental defects and these injury mechanisms are linked to changes in LPA signaling during critical periods of corticogenesis. This chapter will focus on the role of LPA in neurogenesis of the developing brain and the contribution of aberrant LPA signaling and metabolism in the pathogenesis of neurodevelopmental diseases.

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Abbreviations

5-HT:

Serotonin

ATX:

Autotaxin

Ca2+ :

Calcium

cAMP:

Cyclic adenosine monophosphate

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DAG:

Diacylglycerol

E:

Embryonic day

EDG:

Endothelial differentiation gene

EGF:

Epidermal growth factor

Enpp2:

Epidermal growth factor receptor phosphodiesterase family member 2

FABP:

Fatty acid binding protein

GPAT:

Glycerophosphate acyltransferase

GPCR:

G protein-coupled receptor

GRK2:

G protein-coupled receptor kinase 2

HIF-1α:

Hypoxia inducible factor-1 alpha

IZ:

Intermediate zone

LCAT:

Lecithin cholesterol acyltransferase

LP:

Lysophospholipids

LPA:

Lysophosphatidic acid

LPA1–6 :

Lysophosphatidic acid GPCR 1–6

LPAAT:

Lysophosphatidic acid acyltransferase

LPAR1–6:

Human Lysophosphatidic acid GPCR genes 1–6

Lpar1–6:

Mouse Lysophosphatidic acid GPCR genes 1–6

LPC:

Lysophosphatidylcholine

LPP:

Lipid phosphate phosphatases

MAG:

Monoacylglycerol

MAP:

Microtubule-associated protein

NGF:

Nerve growth factor

NPC:

Neuroprogenitor cell

P2Y:

Purinergic family genes

PA:

Phosphatidic acid

PC:

Phosphatidylcholine

PCD:

Programmed cell death

PHH:

Post-hemorrhagic hydrocephalus

PL:

Phospholipids

PLA1:

Phospholipase A1

PLC:

Phospholipase-C

PS:

Phosphatidylserine

PSA-NCAM:

Polysialylated neural cell adhesion protein

PS-PLA1:

Phosphatidylserine-specific phospholipase A1

S1P:

Sphingosine-1-phosphate

SOX2:

Sex determining region Y-box 2

sPLA2:

Secretory phospholipase A2

SVZ:

Subventricular zone

TrkA:

Tyrosine kinase receptor type 1

VEGF:

Vascular endothelial growth factor

VZ:

Ventricular zone

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  1. Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Whitney S. McDonald Ph.D. & Jerold Chun M.D., Ph.D.

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    Alice Pébay

  2. The University of Melbourne & Centre for Eye Research Australia, Melbourne, Victoria, Australia

    Raymond C.B. Wong

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McDonald, W.S., Chun, J. (2017). Lysophosphatidic Acid (LPA) Signaling in Neurogenesis. In: Pébay, A., Wong, R. (eds) Lipidomics of Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-49343-5_4

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