Research article

Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology

Jillian H Hurst¹ , Jennifer Mumaw² , David W Machacek³ , Carla Sturkie² , Phillip Callihan¹ , Steve L Stice^2,3 and Shelley B Hooks^1,4

¹  Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA

²  Regenerative Bioscience Center Animal Science Department, University of Georgia, Athens, GA, USA

³  Aruna Biomedical, Inc., Athens, GA, USA

⁴  377 Wilson Pharmacy Building, 250 West Green Street, Athens, GA 30602-2352, USA

author email corresponding author email

BMC Neuroscience 2008, 9:118doi:10.1186/1471-2202-9-118

Published:	11 December 2008

Abstract

Background

Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP) cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development.

Results

Our results demonstrate that Lysophosphatidic Acid (LPA) and Sphingosine-1-phosphate (S1P) receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to G_i/o G-proteins that inhibit adenylyl cyclase and to G_q-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via G_i/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR)- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK.

Conclusion

Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.