An essential role for LPA signalling in telencephalon development

Geach, Timothy J.; Faas, Laura; Devader, Christelle; Gonzalez‐Cordero, Anai; Tabler, Jacqueline M.; Brunsdon, Hannah; Isaacs, Harry V.; Dale, Leslie

doi:10.1242/dev.104901

Cited by 20 publications

(12 citation statements)

References 72 publications

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“…LPA 6 is the most recently identified member of the LPA receptor family . It has been described that in Xenopus, the LPA 6 receptor is expressed in the developing telencephalon . These results are in line with ours.…”

Section: Discussionsupporting

confidence: 92%

LPA₁, LPA₂, LPA₄, and LPA₆ receptor expression during mouse brain development

Suckau

Gross

Schrötter

et al. 2019

Developmental Dynamics

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Background LPA is a small bioactive phospholipid that acts as an extracellular signaling molecule and is involved in cellular processes, including cell proliferation, migration, and differentiation. LPA acts by binding and activating at least six known G protein–coupled receptors: LPA 1–6 . In recent years, LPA has been suggested to play an important role both in normal neuronal development and under pathological conditions in the nervous system. Results We show the expression pattern of LPA receptors during mouse brain development by using qRT‐PCR, in situ hybridization, and immunocytochemistry. Only LPA 1 , LPA 2, LPA 4, and LPA 6 mRNA transcripts were detected throughout development stages from embryonic day 16 until postnatal day 30 of hippocampus, neocortex, cerebellum, and bulbus olfactorius in our experiments, while expression of LPA 3 and LPA 5 genes was below detection level. In addition to our qRT‐PCR results, we also analyzed the cellular protein expression of endogenous LPA receptors, with focus on LPA 1 and LPA 2 within postnatal brain slices and primary neuron differentiation with and without cytoskeleton stabilization and destabilization. Conclusions The expression of LPA receptors changes depends on the developmental stage in mouse brain and in cultured hippocampal primary neurons. Interestingly, we found that commercially available antibodies for LPA receptors are largely unspecific.

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Section: Discussionsupporting

confidence: 92%

LPA₁, LPA₂, LPA₄, and LPA₆ receptor expression during mouse brain development

Suckau

Gross

Schrötter

et al. 2019

Developmental Dynamics

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“…Lpar6 , the most recently characterized LPAR family member, is enriched in the neural plate of Xenopus neurulae. Deletion of Lpar6 results in forebrain defects with concomitant reduction of telencephalic markers, as well as defects extending into the hindbrain (Geach et al, 2014). The roles of Lpar6 in the development and function of the mammalian nervous system remain to be characterized, although human mutations of this receptor gene have most notably been associated with forms of hair loss (Pasternack et al, 2008).…”

Section: Lparsmentioning

confidence: 99%

Lysophosphatidic Acid Signaling in the Nervous System

Yung

Stoddard

Mirendil

et al. 2015

Neuron

226

177

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Summary The brain is composed of many lipids with varied forms that serve not only as structural components but also as essential signaling molecules. Lysophosphatidic acid (LPA) is an important bioactive lipid species that is part of the lysophospholipid (LP) family. LPA is primarily derived from membrane phospholipids and signals through six cognate G protein-coupled receptors (GPCRs), LPA1-6. These receptors are expressed on most cell types within central and peripheral nervous tissues and have been functionally linked to many neural processes and pathways. This review covers a current understanding of LPA signaling in the nervous system, with particular focus on the relevance of LPA to both physiological and diseased states.

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“…For example, two Xenopus G‐protein coupled purinergic receptors, p2ry1 and p2ry11 , are expressed in the prospective head region and involved in head formation (Harata, Nishida, Nishihara, & Hashimoto, ), and p2ry1 synergistically regulates eye development with the ectonucleoside triphosphate diphosphohydrolase (E‐NTDPase) (Masse, Bhamra, Eason, Dale, & Jones, ). Furthermore, lysophosphatidic acid receptor 6 ( lpar6 ), also known as p2ry5 , is required for forebrain development (Geach et al., ). In X. laevis tadpole, pyrimidinergic receptor P2Y, G‐protein coupled, 4 L homeolog, p2ry4.L , is expressed in basal cells of the main olfactory epithelium and involved in the regulation of cell turnover in the olfactory epithelium (Hassenklover, Schwartz, Schild, & Manzini, ; Hassenklover et al., ).…”

Section: Introductionmentioning

confidence: 99%

Nucleotide receptor P2RY4 is required for head formation via induction and maintenance of head organizer in Xenopus laevis

et al. 2018

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Vertebrates have unique head structures that are mainly composed of the central nervous system, the neural crest, and placode cells. These head structures are brought about initially by the neural induction between the organizer and the prospective neuroectoderm at early gastrula stage. Purinergic receptors are activated by nucleotides released from cells and influence intracellular signaling pathways, such as phospholipase C and adenylate cyclase signaling pathways. As P2Y receptor is vertebrate-specific and involved in head formation, we expect that its emergence may be related to the acquisition of vertebrate head during evolution. Here, we focused on the role of p2ry4 in early development in Xenopus laevis and found that p2ry4 was required for the establishment of the head organizer during neural induction and contributed to head formation. We showed that p2ry4 was expressed in the head organizer region and the prospective neuroectoderm at early gastrula stage, and was enriched in the head components. Disruption of p2ry4 function resulted in the small head phenotype and the reduced expression of marker genes specific for neuroectoderm and neural border at an early neurula stage. Furthermore, we examined the effect of p2ry4 disruption on the establishment of the head organizer and found that a reduction in the expression of head organizer genes, such as dkk1 and cerberus, and p2ry4 could also induce the ectopic expression of these marker genes. These results suggested that p2ry4 plays a key role in head organizer formation. Our study demonstrated a novel role of p2ry4 in early head development.

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An essential role for LPA signalling in telencephalon development

Cited by 20 publications

References 72 publications

LPA₁, LPA₂, LPA₄, and LPA₆ receptor expression during mouse brain development

LPA₁, LPA₂, LPA₄, and LPA₆ receptor expression during mouse brain development

Lysophosphatidic Acid Signaling in the Nervous System

Nucleotide receptor P2RY4 is required for head formation via induction and maintenance of head organizer in Xenopus laevis

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An essential role for LPA signalling in telencephalon development

Cited by 20 publications

References 72 publications

LPA1, LPA2, LPA4, and LPA6 receptor expression during mouse brain development

LPA1, LPA2, LPA4, and LPA6 receptor expression during mouse brain development

Lysophosphatidic Acid Signaling in the Nervous System

Nucleotide receptor P2RY4 is required for head formation via induction and maintenance of head organizer in Xenopus laevis

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LPA₁, LPA₂, LPA₄, and LPA₆ receptor expression during mouse brain development

LPA₁, LPA₂, LPA₄, and LPA₆ receptor expression during mouse brain development