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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 . 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  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 ) of dpp and hh . 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 .
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 . A similar shut-OFF is expected for discs devoid of En, but this condition has yet been created . 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 . (Its ubiquity is shown by the ability of ptcnull A clones to turn ON en .)
N.B.: Events in the boundary zone are more complex than depicted here (cf. Figs. 6.3 - 6.4 - 6.5) -- especially for Ci . 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  -- 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)  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 cinull 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  or Extradenticle [3324, 3325, 3861] or the Trx-G chromatin-remodeling complex (cf. Ch. 8) . 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 . After [2832, 4479, 4539]. See  for further nuances.