The transparency of the Drosophila basal lamina to FGF signaling contrasts with the barrier functionality of the embryo plasma and vitelline membranes. The question arises whether transparency is a general property of basal lamina – whether the basal lamina is also transparent to Hh, Dpp and Wg. No measures of Hh, Dpp or Wg signaling through basal lamina have been reported, but if basal lamina were not transparent, it would presumably bind these proteins to restrict their movement. FGF binds its receptor together with heparan sulfate proteoglycans (HSPGs), one of the major constituents of extracellular matrix and basal lamina, so binding per se is not synonymous with barrier function. Wing disc-associated tracheal cells express components of the Dpp and Wg signal transduction pathways and are sensitive to ectopic expression of these signaling proteins (Li, L., A.G. and T.B.K., unpublished); moreover, development of the disc-associated trachea appears to be Hh-dependent [Li, L. and Kornberg, T.B., unpublished, and 22
]. It seems reasonable to assume, therefore, that tracheal cells have the capacity to respond to Hh, Dpp and Wg if these proteins were to emanate from the disc ().
We propose that Hh, Dpp and Wg move to form their respective gradients in a manner that prevents their contact with cells other than their intended targets. How might this be achieved? One possibility is that morphogen secretion is only apical, thereby preventing secreted morphogens from contacting potential targets such as the tracheals cells that are near the basal surface. Although the literature is not unanimous regarding the polarity of secretion, evidence for apical secretion in wing discs has been reported for Hh [17
], Dpp [18
] and Wg [19
If secretion is apical, how might cross-lumenal signaling be prevented? We consider two scenarios for apical Dpp dispersion (). Dpp is expressed by the anteroposterior organizing signaling centers of the columnar and peripodial surfaces. If it is secreted in a form that diffuses freely, it will move until it is either degraded or is bound by a receptor, co-receptor or other type of binding protein. Unrestricted apical diffusion would presumably lead to activation of targets in both cell layers (). We assume therefore that dispersion is confined to the apical surface of both cell layers, such that it will activate targets only in the layer that produces it ().
Four types of mechanisms have been proposed to explain how morphogens move from source cells to targets in the wing primordium. As schematized in , these are: diffusion in extracellular space [26
]; serial transfers from neighbor to neighbor involving transcytosis and endocytic trafficking [28
]; transfer in lipoprotein particles [5
]; and direct transfer at sites of cytoneme-mediated contacts [30
]. No published experiments definitively establish any of these proposed mechanisms as operative (or inoperative), and it is beyond the scope of this brief essay to review how transcytosis, lipoprotein transfer or direct contact might effect planar dispersion of morphogens. We posit that passive diffusion, whether it is entirely unfettered or involves shuttling between binding moieties in the apical membrane of the epithelial cells [2
], is an unlikely mechanism to move morphogens for long distances in the plane of the epithelium if it cannot prevent them from moving even a short distance out of the plane.
Four models of morphogen dispersion. Movement of morphogen (red) from source cell (middle, purple) to outlying cells by diffusion, serial transfer (transcytosis), lipoprotein particle transfer, and directly (via cytonemes).