Neudesin, a secreted factor, promotes neural cell proliferation and neuronal differentiation in mouse neural precursor cells

Abstract

Neudesin encodes a secreted signal with neurotrophic activity in neurons. Most neurotrophic factors are involved in neural cell proliferation and/or differentiation. However, the role of neudesin in neural development remains to be elucidated. We examined the expression of neudesin in mouse embryonic cerebral cortex and cultured mouse neural precursor cells and its roles in neural development. Neudesin was expressed in the embryonic cerebral cortex early in development. Its expression was observed mainly in the preplate, where mostly postmitotic neural cells existed. Because neudesin mRNA was expressed in the neural precursor cells before the appearance of neurons, the roles of neudesin in neural development were examined by using the precursor cells. Neudesin significantly promoted neuronal differentiation and overrode the undifferentiated state of the neural precursor cells sustained by fibroblast growth factor 2 (FGF2). In contrast, it inhibited the differentiation of astrocytes. In addition, neudesin transiently promoted neural cell proliferation early in the developmental process. The effect on cell proliferation was distinct from that of FGF2, a self-renewal-promoting factor for neural precursor cells. The differentiation was mediated though activation of the protein kinase A (PKA) and phosphatidylinositol-3 kinase (PI-3K) pathways. In contrast, the proliferation was mediated through the mitogen-activated protein kinase and PKA pathways. The expression profile and activity indicate that neudesin plays unique roles in neural development. The present findings have revealed new potential roles of neudesin in neural cell proliferation and neuronal differentiation.

Characterization of Regenerative Phenotype of Unrestricted Somatic Stem Cells (USSC) from Human Umbilical Cord Blood (hUCB) by Functional Secretome Analysis

“…Comparison of all secreted proteins or proteins predicted to be secreted according to the literature revealed that USSC secrete at least 31 proteins that are known to be involved in neurite growth or axonal regrowth (Table I) including the neurotrophic factors mesencephalic astrocyte-derived neurotrophic factor (MANF) (37), neudesin (38), and neuron-derived neurotrophic factor (NDNF) (39) as well as the growth factors angiopoietin-2 (40), growth/differentiation factor 15 (GDF-15) (41), hepatoma-derived growth factor (HDGF) (42), PDGF (43), and transforming growth factor-beta1/-2 (TGF-␤1/TGF-␤2) (44 -45). Moreover, we identified several matrix-and membrane-associated proteins, e.g.…”

“…PDGF and TGF-␤1, both secreted by USSC, are known to interact with SPARC (64 -66), indicating a solid network between the secreted factors. Moreover, USSC secrete MIF, which directs the initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear (56), and NDNF, which could together with MANF, HDGF, and neudesin stimulate neurite growth as well as migration, cell growth, and survival (37)(38)(39)42). Recently, periostin, which is normally expressed in bone and muscles, has been shown to play an essential role in neurite growth and axonal regeneration after SCI to overcome the inhibitory effect of scar-associated molecules by signaling through focal adhesion kinase and Akt (67).…”

Neurotrophic Activity of Neudesin, a Novel Extracellular Heme-binding Protein, Is Dependent on the Binding of Heme to Its Cytochrome b5-like Heme/Steroid-binding Domain

“…Neudesin is the novel secreted protein that we previously identified as a neurotrophic factor (12,13). Mouse neudesin exhibited high similarity (ϳ90% identity) to human and rat neudesins.…”

The evolutionary appearance of signaling motifs in PGRMC1

“…This may be because Neudesin and Neferricin are present in the luminal compartment and secreted extracellularly (2,3,(24)(25)(26)(27)(28), however the presence of some observed phosphorylation events suggests that the MAPR domain of these proteins may also be found in the cytoplasm. The detection of O-N-acetylgalactosamine (O-GalNAc) glycosylation does not necessarily imply an extracellular location for Neudesin, since 14% of O-GalNAc proteins are annotated with nuclear Gene Ontogeny (GO) assignments (29).…”