Paracrine Pax6 activity regulates oligodendrocyte precursor cell migration in the chick embryonic neural tube

Abstract

Homeoprotein transcription factors play fundamental roles in development, ranging from embryonic polarity to cell differentiation and migration. Research in recent years has underscored the physiological importance of homeoprotein intercellular transfer in eye field development, axon guidance and retino-tectal patterning, and visual cortex plasticity. Here, we have used the embryonic chick neural tube to investigate a possible role for homeoprotein Pax6 transfer in oligodendrocyte precursor cell (OPC) migration. We report the extracellular expression of Pax6 and the effects of gain and loss of extracellular Pax6 activity on OPCs. Open book cultures with recombinant Pax6 protein or Pax6 blocking antibodies, as well as in ovo gene transfer experiments involving expression of secreted Pax6 protein or secreted Pax6 antibodies, provide converging evidences that OPC migration is promoted by extracellular Pax6. The paracrine effect of Pax6 on OPC migration is thus a new example of direct non-cell autonomous homeoprotein activity.

A novel role for Pax6 in the segmental organization of the hindbrain

“…Interestingly, in addition to its established cellautonomous roles, Pax6 has demonstrated an unexpected paracrine effect in different CNS tissues (Di Lullo et al, 2011;Lesaffre et al, 2007). Whether Pax6 acts similarly in the early hindbrain is not known and requires further understanding of how Pax6 acts as a signaling molecule.…”

Postnatal signalling with homeoprotein transcription factors

“…It was shown that En1/2 cooperates with EphrinA5 in the optic tectum and with DPP in the fly wing disc [14,16,17]. A similar synergy was found between Pax6 and Netrin signalling in the ventral neural tube [13]. The essence of this synergy, illustrated in figure 3, is based on the hypothesis that HPs sensitize the classical receptors to otherwise inefficient concentrations of their agonists.…”

“…Blocking the passage of Pax6 in vivo by local expression of a single-chain antibody (aPax6-scfv) or by injection of a monoclonal anti-Pax6 antibody at the midblastula stage prevents the extension of the eye anlagen in the zebrafish and leads to defects in eye development [12]. Another recently discovered non-cell-autonomous embryonic function of Pax6 is to enhance oligodendrocyte precursor cell migration in the chick neural tube [13].…”

Homeoprotein Signaling in Development, Health, and Disease: A Shaking of Dogmas Offers Challenges and Promises from Bench to Bed

“…Indeed, this does not mean that they actually do it or that in vitro results can be generalized to in vivo situations. However, intercellular transfer has been demonstrated in vivo for Engrailed1, Engrailed2, Otx2, and Pax6, the four proteins that were analyzed from a physiologic point of view (Lesaffre et al, 2007;Sugiyama et al, 2008;Wizenmann et al, 2009;Di Lullo et al, 2011;Beurdeley et al, 2012;Yoon et al, 2012). Thus, we are confident that HP signaling is a very general and important phenomenon.…”

“…In vivo, the situation might be different because of the presence of HP binding sites (Beurdeley et al, 2012) that can trap the proteins and regulate their internalization. From this point of view, of note, whenever the quantification was done, ;5% of the HPs were at the cell surface, compared with 95% in the intracellular compartments (Wizenmann et al, 2009;Di Lullo et al, 2011) …”