Table of contents

• Preface

• Chapter One Cell Lineage vs. Intercellular Signaling
  • Discs are not clones.
  • No part of a disc is a clone, except claws and tiny sense organs.
  • Cells belong to lineage "compartments".

• Chapter Two The Bristle

  • Numb segregates asymmetrically and dictates bristle cell fates.
  • Delta needs to activate Notch, but not as a signal per se.
  • Amnesic cells can use sequential gating to simulate a binary code.
  • Notch must go to the nucleus to function.
  • E(spl)-C genes are Su(H) targets but play no role in the SOP lineage.
  • The transcription factor Tramtrack implements some cell identities.
  • Hairless titrates Su(H).
  • Several other genes help determine the 5 cell fates.
  • Pox neuro and Cut specify bristle type.
  • Bract cells are induced by bristle cells.
  • Macrochaetes and microchaetes differ in size but not in kind.

• Chapter Three Bristle Patterns
  • Surprisingly, different macrochaete sites use different signals.
  • Prepatterns may contain hidden "singularities".
  • How Achaete and Scute control bristles was debated for decades.
  • In 1989, Achaete and Scute were found to mark "proneural clusters".
  • In 1995, the old AS-C paradigm toppled and a new one emerged.
  • Proneural "spots" shrink to SOP "dots".
  • The SOP uses a feedback loop to raise its Ac and Sc levels.
  • Two other bHLH genes (asense and daughterless) assist SOPs.
  • "Lateral" or "mutual" inhibition ensures one SOP per PNC.
  • Notch-pathway and proneural genes are functionally coupled.
  • Doses of Notch-pathway genes can bias the SOP decision.
  • Extra SOPs could be inhibited by contact or diffusion (or both).
  • Scabrous may be the diffusible SOP inhibitor.
  • Inhibitory fields dictate the spacing intervals of microchaetes.
  • Microchaetes come from proneural stripes, not spots.
  • Hairy paints "antineural" stripes on the legs.
  • Leg bristles use extra fine-tuning tricks.
  • Chemosensory leg bristles are patterned like notal macrochaetes.
  • Extramacrochaetae superimposes an uneven antineural "mask".
  • Dose dependency implies that HLH proteins "compute" bristles.
  • Robustness of patterning may be due to a tolerant time window.
  • Atonal and Amos are proneural agents for other types of sensilla.
  • Other (upstream) pathways govern bristle patterning.

• Chapter Four Origin and Growth of Discs
  • Segmentation genes set the stage for disc initiation.
  • Prepatterns and gradients clashed in trying to explain homeosis.
  • Homeotic genes implement regional identities.
  • Wing and haltere discs "grow out" from 2nd- and 3rd-leg discs.
  • Thoracic discs arise at Wingless/Engrailed boundaries.
  • Cell lineage within compartments is indeterminate.
  • The Polar Coordinate Model linked regeneration to development.
  • But regeneration has peculiarities that set it apart.

• Chapter Five The Leg Disc
  • The Molecular Epoch of disc research was launched in 1991.
  • BatesonÌs Rule (1894) governs symmetry planes in branched legs.
  • MeinhardtÌs Boundary Model deftly explained BatesonÌs Rule.
  • The Boundary and PC Models jousted in a "Paradigm War".
  • Hh, Dpp, and Wg are the chief intercellular signaling molecules.
  • P-type cells use Hh to "talk" to A-type cells nearby.
  • Hh elicits expression of Dpp and Wg along the A/P boundary.
  • Dpp dorsalizes and Wg ventralizes, or do they?
  • Dpp and Wg are mutually antagonistic.
  • Dpp and Wg jointly initiate distal outgrowth.
  • But Dpp seems more crucial than Wg as a growth factor.
  • The A/P boundary can migrate when its "jailors" are "asleep".
  • Regeneration is due to a Hh spot in the peripodial membrane.
  • The Polar Coordinate Model died in 1999.
  • How Hh, Dpp, and Wg move is not known, nor is their range.
  • Whether Dpp and Wg travel along curved paths is not known.
  • Hairy links global to local patterning.
  • Questions remain about the Hh-Dpp-Wg circuitry.
  • Distal-less is necessary and sufficient for distalization.
  • Proximal and distal cells have different affinities.
  • Dachshund is induced at the Homothorax/Distal-less interface.
  • Homothorax and Extradenticle govern the proximal disc region.
  • Fasciclin II is induced at the BarH1/Aristaless interface.
  • BarH1 and Bric à brac affect P-D identity, joints, and folds.
  • Leg segmentation requires Notch signaling.

• Chapter Six The Wing Disc
  • The A-P axis is governed by Hh and Dpp but not by Wg.
  • Dpp turns on omb and spalt at different thresholds.
  • Dpp regulates omb and spalt similarly despite clues to the contrary.
  • Dpp does not regulate tkv in 3rd instar despite clues to the contrary.
  • A vs. P identities might explain how a straight A/P line emerges.
  • But the A/P line appears to straighten via a signaling mechanism.
  • Intercalation is due to a tendency of Dpp gradients to rise.
  • The variable height of Dpp gradients makes them appear seamless.
  • A Wg gradient specifies cell fates along the wingÌs D-V axis.
  • Perpendicular (Dpp x Wg) gradients suggest Cartesian coordinates.
  • But cells do not seem to record positional values per se.
  • WgÌs repression of Dfz2 is inconsequential.
  • ApterousÌs role along the D-V axis resembles EngrailedÌs A-P role.
  • Chip cooperates with Apterous, and "Dorsal wing" acts downstream.
  • Serrate and Delta prod Notch to evoke Wg at the D/V line.
  • Fringe prevents Notch from responding to Serrate.
  • The core D-V circuit plugs into a complex network.
  • The wing-notum duality is established by Wg and Vein.
  • But Vestigial and Scalloped dictate "wingness" per se.
  • Straightening of the D/V border requires Notch signaling and Ap.
  • Straightening of veins may rely on similar tricks.
  • Two cell types predominate in the wing blade: vein and intervein.
  • Veins come from proveins that look like proneural fields.
  • But the resemblance is only superficial.
  • All veins use the EGFR pathway.
  • But interveins also use the EGFR pathway (at a later time).
  • Veins 3 and 4 are positioned by the Hh pathway.
  • Veins 2 and 5 are positioned by the Dpp pathway.
  • The Dpp pathway later implements the vein state.
  • A cousin of Dpp (Gbb) fosters the A and P cross-veins.
  • Vein 1 uses a combination of Dpp and Wg signals.
  • Macrochaetes are sited by various "prepattern" inputs.
  • How bristle axons get wired into the CNS is not known.

• Chapter Seven The Eye Disc
  • Compound eyes have ~750 facets, with 8 photoreceptors per facet.
  • Unlike the bristle, the ommatidium is not a clone.
  • The eye has D and V compartments (despite doubts to the contrary).
  • The Iroquois Complex controls D-V polarity via Fringe and Notch.
  • A morphogenetic wave creates the ommatidial lattice.
  • D-V polarity depends on a rivalry between R3 and R4 precursors.
  • R1-R8 cells arise sequentially, implying a cascade of inductions.
  • But the final cell (R7) is induced by the first one (R8).
  • Various restraints prevent more than one cell from becoming R7.
  • The information content of the inductive signals may be only 1 bit.
  • No transcription factor "code" has yet been found for R cells.
  • The lattice is created by inhibitory fields around R8 precursors.
  • The lattice is tightened when excess cells die.
  • Eye bristles arise independently of ommatidia.
  • The MF operates like a moving A/P boundary.
  • Dpp and Wg control the rate of MF progress.
  • The MF originates via different circuitry.

• Chapter Eight Homeosis
  • BX-C and ANT-C specify gross metameric identities along the body.
  • Ubx enables T3 discs to develop differently from T2 discs.
  • But Ubx does so by directly managing target genes in multiple echelons.
  • Pc-G and Trx-G "memory" proteins keep homeotic genes on or off.
  • Homothorax, Distal-less, and Spineless specify leg vs. antennal fates.
  • If a "master gene" exists for the eye, then it is also a micromanager.
  • The manifold "enhanceosome" is a wondrous Gordian Knot.
  • The deepest enigma is how evolution rewired the circuit elements.

• Epilogue

• Appendix 1 Glossary of Protein Domains

• Appendix 2 Inventory of Models, Mysteries, Devices, and Epiphanies

• Appendix 3 Genes That Can Alter Cell Fates Within the (5-Cell) Mechanosensory Bristle Organ

• Appendix 4 Genes That Can Transform One Type of Bristle Into Another or Into a Different Type of Sense Organ

• Appendix 5 Genes That Can Alter Bristle Number by Directly Affecting SOP Equivalence Groups or Inhibitory Fields

• Appendix 6 Signal Transduction Pathways: Hedgehog, Decapentaplegic, and Wingless

• Appendix 7 Commentaries on the Pithier Figures

• References

• Index

Imaginal Discs Index

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