Eph/Ephrin Signaling Controls Progenitor Identities in the Ventral Spinal Cord

Abstract

2 SUMMARY STATEMENTThis article by Laussu et al. describes a role for Eph:ephrin signaling in controlling the identity of neural progenitors in the ventral spinal cord. ABSTRACTEarly specification of progenitors of the ventral spinal cord involves the morphogen Sonic Hedgehog which induces distinct progenitor identities in a dose-dependent manner. Following these initial patterning events, progenitor identities have to be maintained in order to generate appropriate numbers of progeny. Here we provide evidence that communication viaEph:ephrin signaling is required to maintain progenitor identities in the ventral spinal cord.We show that ephrinB2 and ephrinB3 are expressed in restricted progenitor domains in the ventral spinal cord while several Eph receptors are more broadly expressed. Further, we provide evidence that expression of Efnb3 and EphA4 is controlled by Shh. Genetic loss-offunction analyses indicate that expression of ephrinB2 and ephrinB3 is required to control progenitor identities and in vitro experiments reveal that activation of Eph forward signaling in spinal progenitors up-regulates the expression of the identity transcription factor Nkx2.2.Altogether our results indicate that cell-to-cell communication is necessary to control progenitor identity in the ventral spinal cord.

Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells Are Functionally and Genetically Different From Bone Marrow-Derived Mesenchymal Stromal Cells

“…Mesengenesis of iPSCs by inhibiting TGF‐β/Activin/Nodal signaling with SB‐431542 resulted in a greater expression of VEGFR1 ( FLT1 ), a marker of vascular endothelial cells in iMSCs than in BM‐MSCs . Mesengenic induction using FGF2 and PDGF followed by cell sorting for a CD105 + CD24 − population also gave rise to a heterogeneous culture with greater expression of vascular endothelial markers ( CL‐P1 and FAM43A ) and neuroprogenitor markers ( EFNB3 , SLITRK5 , and CKAP2L ) in ESC‐MSCs than in BM‐MSCs . Moreover, irrespective of the derivation methods used, extremely low expression of MSC‐associated genes was often detected in these PSC‐MSCs, including IL6 , BST1 , SFRP4 , and VCAM1 .…”

EphrinB2 signalling modulates the neural differentiation of human dental pulp stem cells

“…Previous studies in animal models have demonstrated the role of EphrinB2 signalling in the lineage specification of motor neurons in the spinal cord (13) and dopaminergic neurons in the midbrain (15). Nevertheless, there are contradictory and conflicting data within the scientific literature regarding the role of EphrinB2 signalling in both the promotion and inhibition of the differentiation of neural stem cells and neural progenitors.…”

“…The signalling pathways mediated by the family of EphB receptors and EphrinB ligands, which are expressed in the perivascular niche of the dental pulp, are known to serve key roles in the proliferation, mobilization and mineralization of DPSCs during the process of tooth regeneration, in response to injury of the dentin matrix (12). Of particular interest in the field of neuroregeneration are EphrinB2 and its cognate receptors EphB2 and EphB4, which have been demonstrated to serve key developmental roles in embryonic neurogenesis (13)(14)(15) as well as in the homeostasis and mobilization of neural stem cells (16) and neural progenitors (17). EphrinB2 and its cognate receptors EphB2 and EphB4 are transmembrane receptor tyrosine kinases, which are established to play crucial roles in cell migration and in the determination of cell lineage fate (18).…”

Evolution of vertebrate spinal cord patterning

“…The ventral spinal cord is dependent on the morphogen Shh secreted from the floorplate and notochord, evidenced by failure of ventral spinal cord patterning in Shh −/− mice . Other factors may also have contributions to ventral patterning including Eph/Ephrin signaling, and Chordin , which is expressed in the notochord and inhibits Bmp signaling, but Hedgehog (Hh) signaling mediated by Shh has a dominant role. Pairs of cross‐repressive transcription factor genes lie downstream of the Shh signal.…”