Autotaxin controls caudal diencephalon‐mesencephalon development in the chick

Abstract

The diencephalon is the embryonic anlagen of the higher integration centers of the brain. Recent studies have elucidated how the cells in the rostral diencephalon acquire their regional identities. However, the understanding of the mechanisms under which the caudal diencephalon is formed is still limited. Here we focus on the role of Autotaxin (ATX), a lysophospholipid-generating exoenzyme, whose mRNA is detected in the caudal diencephalon. RNA interference against ATX altered the expression pattern of Pax6-regualted genes, Tcf4, Lim1, and En1, implying that ATX is required for the maintenance of the regional identity of the caudal diencephalon and the diencephalon-mesencephalon boundary (DMB). Furthermore, ATX-RNAi inhibited neuroepithelial cell proliferation on both sides of the DMB. We propose a dual role of ATX in chick brain development, in which ATX not only contributes to the formation of caudal diencephalon as a short-range signal, but also regulates the growth of mesencephalon as a long-range signal. Developmental Dynamics 239:2647-2658,

G-Protein-Coupled Receptor Cell Signaling Pathways Mediating Embryonic Chick Retinal Growth Cone Collapse Induced by Lysophosphatidic Acid and Sphingosine-1-Phosphate

“…In Xenopus , S1P or a sphinogosine kinase inhibitor affected the growth of RGC axons into the tectum [22], suggesting that S1P may be involved in mediating retinal ganglion cell axon entry into the tectum. Furthermore, autotaxin, a major enzyme responsible for LPA production, is expressed strongly in caudal diencephalon [72,73], suggesting that LPA could be responsible for preventing retinal ganglion cell axon growth beyond the tectum. There is also the possibility that LPA and/or S1P may be involved in topographic mapping of RGC axons to the tectum, although preliminary evidence suggests that this may not be the case.…”

Lack of lipid phosphate phosphatase‐3 in embryonic stem cells compromises neuronal differentiation and neurite outgrowth

“…On the other hand, gene inactivation of LPA and S1P metabolizing enzymes has profound effects on early NS development. Autotaxin ( Atx ) targeted inactivation suggested that it plays important roles in anterior brain morphogenesis and establishment of the MHB (Ohuchi et al, 2010; Koike et al, 2011). In addition Atx conditional inactivation in the epiblast produced defective neural tube closure, decreased neuroepithelium proliferation, increased cell death and reduction in the amount of differentiated young neurons (Tanaka et al, 2006; van Meeteren et al, 2006; Fotopoulou et al, 2010).…”

“…Furthermore, in Xenopus laevis sphingosine kinase-1 expression limits the pathway by which retinal axons grow from the optic chiasm to the tectum and either gain or loss of S1P function in vivo causes errors in axon navigation (Strochlic et al, 2008). It has also been shown that autotaxin ( Atx ), the main extracellular-LPA synthesizing enzyme, contributes to anterior brain morphogenesis and establishment of the midbrain-hindbrain boundary (MHB) (Ohuchi et al, 2010; Koike et al, 2011). Another report indicates that in a neurosphere culture system, 1 μM of LPA increases the number of MAP2-positive neurons and decreases the proportion of myelin basic protein-positive oligodendrocytes in cortical neuroblasts (Fukushima et al, 2007).…”

Role of Ectonucleotidases in Synapse Formation During Brain Development: Physiological and Pathological Implications

“…The involvement of NPP2 in oligodendrocyte development may mainly result from its lysophospholipase D activity and an additional functional domain mediating the modulation of oligodendrocyte remodeling and focal adhesion organization [52], a property independent of its catalytic activity [52, 53]. The importance of NPP2 in brain development is underscored in chick embryos studies, where it regulates the maintenance of the diencephalon–mesencephalon boundary and neuroepithelial cell proliferation [54]. Interestingly, the chick embryonic brain expresses a C-terminally truncated NPP2 splice variant that lacks catalytic activity.…”