Abstract
Cell-to-cell communication is fundamental for embryo development and subsequent tissue homeostasis. This communication is often mediated by a small number of signaling pathways in which a secreted ligand binds to the surface of a target cell, thereby activating signal transduction. In vertebrate neural development, these signaling mechanisms are repeatedly used to obtain different and context-dependent outcomes. Part of the versatility of these communication mechanisms depends on their finely tuned regulation that controls timing, spatial localization, and duration of the signaling. The existence of secreted antagonists, which prevent ligand–receptor interaction, is an efficient mechanism to regulate some of these pathways. The Hedgehog family of signaling proteins, however, activates a pathway that is controlled largely by the positive or negative activity of membrane-bound proteins such as Cdon, Boc, Gas1, or Megalin/LRP2. In this review, we will use the development of the vertebrate retina, from its early specification to neurogenesis, to discuss whether there is an advantage to the use of such regulators, pointing to unresolved or controversial issues.
Highlights
The highest functions of the nervous system are based on communication among the huge variety of cells that compose the vertebrate brain
Communication among cells is fundamental for correct development of the nervous system
There are several ways in which neural cells exchange information, communication mediated by families of signaling molecules such as Wnt, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Hedgehog (Hh) is one of the most common
Summary
The highest functions of the nervous system are based on communication among the huge variety of cells that compose the vertebrate brain. The precise mechanism by which this happens is still unrefined; when mis-expressed close to the optic recess midline (a Shh source), Cdon binds Shh with great efficacy and serves as a sink to limit ligand availability to the nearby cells[40] This indicates that Cdon acts as a decoy receptor to protect the neural retina from Hh activity (Figure 2A). Abbreviations Bmp, bone morphogenetic protein; Boc, Brother of Cdon; Cdon, cell adhesion molecule-related, downregulated by oncogenes; CMZ, ciliary marginal zone; CNS, central nervous system; Gas[1], growth arrest protein 1; Hh, hedgehog; Hhip, hedgehog-interacting protein; HPE, holoprosencephaly; LRP2, low-density lipoprotein receptor-related protein 2; Pax[2], paired box protein Pax-2; Pax[6], paired box protein Pax-6; Ptch, patched; RGC, retinal ganglion cell; Shh, sonic hedgehog; Smo, smoothened.
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