Figure 5.7
Effects of Hh diffusion into the A compartment of thoracic discs. For gene abbreviations see text.
a. Left leg and wing discs, with D-V axes of the central regions oriented vertically (cf. compass). A and P compartments are lightly or darkly shaded respectively. The boxed areas of both discs obey the 'Hh —> Dpp' link, but the ventral part of the leg disc obeys 'Hh —> Wg' instead (not shown).

b. Part of the disc epithelium that straddles the A/P compartment boundary (magnified from a). Hexagons are cells (though packing is not so orderly). Cells in the P region express the transcription factor En, while A cells do not. Zigzag line marks the anterior limit of the dpp-ON zone.

c. Circuitry of genes and proteins (abridged; cf. Fig. 5.6) that operates in each of the cell types delineated in b. The chain of events (right to left) starts with expression of en in all P cells. (P cells have Smo but not Ci or Ptc [1022, 2832].) En activates hh but represses ci and dpp [1647, 2832, 2980, 3747, 4227]. Hh diffuses ~8-10 cell diameters into the A region [4136]. Binding of its receptor Patched (Ptc) triggers synthesis and release of Dpp, which turns ON genes like omb (cf. Fig. 6.3) [2455, 3074]. The 'Hh —> Dpp' link is mediated by the transcription factor Ci (horizontal bar). Full-length Ci (155 kD, 1396 a.a.) has 5 tandem zinc fingers (Zn), a C-terminal domain that binds the co-activator dCBP, a proteasome cleavage site (zigzag line), 5 residues capable of phosphorylation by Protein Kinase A (vertical lines) and other domains (cf. text) [54, 2832]. A-type cells do not express dpp in the absence of Hh (left) because basal transcription of ptc [4136] supplies enough Ptc to derepress PKA (via Smo). Phosphorylation of Ci by PKA leads to Ci's proteasome-dependent cleavage, and the N-terminal fragment Ci-75 acts as a repressor (due to an alanine-rich section [65]) of dpp and hh [2832]. Dpp and Hh are both diffusible (triangles denote gradients), but Dpp's range is greater (cf. Fig. 6.3). Omitted here is the enigmatic transcriptional regulation of ci by the zinc-finger protein Combgap (Cg) [621, 4017, 4217]: Cg —> ci throughout the A region of wing and leg discs, but Cg —| ci in the P region of wing (but not leg) discs. Curiously, the En —> hh link is inoperative in the developing eye [4168].

d. Summary of ON/OFF states (thick vs. thin lines) of en, ci, and dpp. The dpp-ON stripe is evidently 'painted' in two ways: (1) directly via 'Hh —> dpp' and (2) indirectly by a figure-ground illusion [657, 1585, 3747] where 'Ci-75 —| dpp' anteriorly and 'En —| dpp' posteriorly. Both actions stem from the disc's en-ON/OFF duality.

Validation of this logic comes from larvae carrying an en transgene driven by a heat-shock promoter. When such larvae are heat-shocked, every cell transiently becomes en-ON (P-type), and the dpp-ON stripe disappears [3747]. A similar shut-OFF is expected for discs devoid of En, but this condition has yet been created [1839]. Not shown is a trespass of the en-ON edge into the border zone that occurs in late 3rd instar when a 'Hh —> en' link pervades the disc [1647]. (Its ubiquity is shown by the ability of ptc^null A clones to turn ON en [4136].)

N.B.: Events in the boundary zone are more complex than depicted here (cf. Figs. 6.3 - 6.4 - 6.5) -- especially for Ci [4540]. En's inhibition of dpp (En —| dpp) occurs both directly (by binding of En to dpp's cis-enhancers [2980, 3747]) and indirectly via En's suppression of ci (since Ci-155 —> dpp [1827, 2832]). Suppression of ci is also partly mediated by Polyhomeotic [3512] -- a member of the Polycomb Group of repressors (cf. Ch. 8) [1012, 1867, 2374]. En's activation of hh (En —> hh) is probably indirect (En —| X? —| hh) [224] since En normally acts a repressor [2047, 2048, 3175, 3860, 4003] by recruiting Groucho [1243, 2064, 4351] (but see [1706, 2642, 2729, 3481]). 'X' is probably not Ci-75 because ci^null clones in the A region do not turn ON hh at P-type levels [1078, 2832, 2834]. Alternatively, En might turn ON hh by using a co-activator such as Blistered [2729] or Extradenticle [3324, 3325, 3861] or the Trx-G chromatin-remodeling complex (cf. Ch. 8) [451]. En is potentially secretable [811, 2085, 2661] but is not used thusly here. Slimb helps keep wg OFF in the P region (not shown) via an Hh-independent route [2856]. After [2832, 4479, 4539]. See [2834] for further nuances.