Control of compartmental affinity boundaries by Hedgehog

Abstract

In Drosophila, each segmental primordium is subdivided into two cell populations, the anterior (A) and posterior (P) compartments by the selective activity of the transcription factor Engrailed (En) in P cells. Under En control, P cells secrete, but cannot respond to, the signalling protein Hedgehog (Hh). In contrast, and by default, A cells are programmed to respond to Hh by expressing other signalling molecules, such as Decapentaplegic (Dpp) and Wingless (Wg), which organize growth and patterning in both compartments. Cells of the A and P compartments do not intermix, apparently as a consequence of their having distinct cell affinities that cause them to maximize contact with cells of the same compartment, while minimizing contact with cells from the other compartment. This failure to mix has previously been ascribed to an autonomous and direct role for En in specifying a P, as opposed to an A, cell affinity. However, an alternative hypothesis is that Hh secreted by P cells induces A cells to acquire a distinct cell affinity, ensuring that a stable 'affinity boundary' forms wherever P and A cells meet. Here we show that the affinity boundary that segregates A and P cells into adjacent but immiscible cell populations is to a large extent a consequence of local Hh signalling, rather than a reflection of an intrinsic affinity difference between A and P cells.

Establishment and maintenance of compartmental boundaries: role of contractile actomyosin barriers

“…1a) [78,79]. Dpp/TGFb signalling then cooperates with Engrailed and Hedgehog signalling to maintain the A/P boundary [24,[26][27][28]. Actomyosin cabling downstream of these factors has not been directly evaluated.…”

“…Alternately, an additional signal could act redundantly with Wingless. Bidirectional signalling is necessary to implement cell sorting at the Drosophila wing disc D/V boundary (Notch/Notch) and A/P boundary (Dpp/Hh), as well as at vertebrate rhombomeres boundaries (Eph/Ephrin) [24,[26][27][28][29][30][35][36][37]. Because actomyosin accumulates asymmetrically at the interfaces of parasegmental boundary cells [50], bidirectional signalling might be involved here as well.…”

“…Because actomyosin accumulates asymmetrically at the interfaces of parasegmental boundary cells [50], bidirectional signalling might be involved here as well. Given that the segment-polarity gene hedgehog, whose expression is dependent on Wingless signalling, is expressed in posterior compartments and controls cell sorting at wing disc A/P boundaries [24,26,27], it is tempting to speculate that Wg/Hh bidirectional signalling controls cell sorting at embryonic A/P boundaries. This hypothesis will, however, require experimental support in the future.…”

“…The Engrailed transcription factor, which confers posterior identity, positions the A/P boundary in cooperation with Hedgehog signalling (Fig. 1a) [24][25][26][27]. Note that Dpp/ TGFb, a long-range signal, is also required to maintain this boundary [28].…”

Hedgehog signaling in vertebrate and invertebrate limb patterning

“…Hh signaling also induces expression of en in this region, where it controls the identity of marginal bristles [31,32]. Although studies of hh function in wing patterning have focused on its role in anterior-posterior patterning and cell fate determination, recent studies have suggested that hh plays an important role in preventing cell mixing between the anterior and posterior compartments, a function originally attributed to en [33,34]. Clones of cells that lack en do not respect compartment boundaries, leading to the suggestion that en might cell-autonomously regulate adhesive properties of posterior cells, thereby preventing them from intermixing with anterior cells.…”