Developmental Compartments

Abstract

Developing tissues are in some cases subdividing into developmental compartments. These are spatially restricted regions between which proliferating and migrating cells cannot mix, even though cells in adjacent compartments can be immediate neighbours in a single epithelium or mesenchyme. Compartments not only serve to subdivide tissues but also, through signalling between compartments, often establish boundary zones that themselves become organising centres for the tissue. First described in the fruit fly Drosophila melanogaster, examples have also been described in vertebrate tissues including the neuroepithelium and limb bud. To establish compartments, cells must retain stable compartmental properties that restrict intermixing of cell lineages at compartmental boundaries. A great deal is now known both about the specification of compartmental cells and their impact on patterning, but much remains to be learned especially about the molecular basis of cell segregation.

Key Concepts

  • Developmental compartments require that cells acquire stable regional identities and have mechanisms that prevent intermixing with unlike cells.
  • Sharply defined regions in developing tissues are not necessarily compartments: cells can also maintain regions using regionalised signalling to change their identities.
  • Techniques for tracing cell lineages, each with its own advantages and pitfalls, are required to establish the existence of a compartment.
  • Compartmental cell identities can be specified by the expression of one or two selector transcription factors or by more complex combinations.
  • Cell segregation can require the establishment of compartment boundary cells.
  • Several alternative mechanisms have been proposed to segregate cells between specific developmental compartments.
  • The most well‐defined molecular mechanism for compartmental cell segregation is the Eph–Ephrin signalling of the rhombomeres of the vertebrate hindbrain.

Keywords: cell lineage; cell specification; selector gene; imaginal disc; rhombomere; limb bud

Figure 1. (a) Alternative methods for sharpening a ragged boundary between two cell types. In the top alternative, the misplaced cell (bold outline) recognises its abnormal position and changes its identity to match that of its neighbours. In the bottom alternative the misplaced cell intercalates between cells with a similar identity. (b) Increasing tissue complexity by intercompartmental signalling to alter the identity of boundary cells and boundary cell signalling to alter the identity of cells within compartments.
Figure 2. Lineage tracing by DNA (deoxyribonucleic acid) recombination. (a,b) Genetically marking progenitor cells using recombination between homologous chromosomes during mitoses in Drosophila. (a) Heterozygous cells carry a marker gene on one of the two homologues. X‐rays or γ‐rays can induce recombination between the marker‐carrying arm of the two homologues, which after mitosis creates progeny that either have lost or have two copies of the marker gene. In imaginal discs, the progeny of these cells often create distinct patches or ‘clones’ of marked cells. (b) The Minute technique uses similar mitotic recombination to create wild‐type, fast‐dividing progeny in a slow‐dividing, wild‐type/Minute tissue, allowing the wild‐type clone to define a longer portion of the compartmental boundary. As an alternative to irradiation (not shown), mitotic recombination can instead be induced by the DNA recombinase FLPase and FLPase recombinase target (FRT)‐bearing chromosomes (Blair, ). However, the greatly increased rate of mitotic recombination achieved with this alternative also increases the chances of confusing the progeny of different progenitors. (c,d) Genetically marking progenitor cells using DNA recombinase expression to unblock expression of marker genes. (c) Low‐level heat‐shock promoter‐driven expression of FLPase causes recombination in a small percentage of cells. (d) Regional expression of recombinase, driven either directly with enhancer or gene insertion constructs or indirectly with regional Gal4 expression driving expression of UAS‐coupled recombinase, triggers recombination in all cells expressing the recombinase. FLPase is typically used in Drosophila, and Cre in mice, although other systems exist.
Figure 3. Compartments in the wing imaginal disc of Drosophila. (a) Wing disc showing subdivision into A/P (anteroposterior) and D/V (dorsoventral) compartments by the posterior expression of the selector transcription factors (t. factors) En–Inv (blue) and the dorsal expression of Ap (yellow). (b) Posterior cells lacking the posterior selectors en–inv, created by mitotic recombination, cross into anterior if next to the A/P boundary, or make smooth boundaries if trapped in the posterior. (c) Hedgehog (Hh) signals from posterior to anterior cells, inducing boundary cells on the anterior side of the A/P boundary. Boundary cells lacking Hh signal reception through loss of smoothened (smo) move into posterior territory without gaining en–inv expression, although they also make abnormally smooth boundaries with posterior cells. (d) Dorsal cells lacking the dorsal selector ap (ap) cross into ventral territory. Notch (N) signalling is high in boundary cells on both sides of the D/V lineage restriction; cells lacking N cross or straddle the D/V boundary without changing their state of ap expression.
Figure 4. Dorsal closure of the segmented ectoderm in a Drosophila embryo, showing the expansion of the ventral germ band towards the dorsal midline. Detail on right shows selective attachment of filopodia from the matching compartment on the other side of the dorsal midline.
Figure 5. Rhombomere compartments in the vertebrate hindbrain. (a) Early ragged boundaries of Krox20 expression in rhombomeres r3 and r5 refine into smooth boundaries using cues from Eph expression in r3 and r5 and Ephrin expression in r4. (b) Changes in cell sorting after gain‐of‐function and loss‐of‐function experiments with binding partners Eph4A and Ephrin2a. The segregation of cells overexpressing Eph4A of EphrinB2a is consistent with Eph–Ephrin signalling driving repulsion. The segregation of cells lacking Eph4A or Ephrin2a is more difficult to explain with a repulsion‐based mechanism (see text). (c) High Notch signalling at rhombomere boundaries and sorting of cells towards or away from those boundaries with gains or losses in Notch signalling, respectively.
Figure 6. Models of cell sorting between compartments. (a) Boundary zone of nondividing cells (bold outlines) acts as trap that limits the challenge to the lineage boundary. (b) Adhesion or attraction between cells within each compartment (green or blue arrows), but not between cells in different compartments, reduces intermixing between compartments. (c) Repulsion between cells from different compartments (orange arrows) reduces intermixing between compartments. (d) Heightened tension (blue outlines) at the cells faces where compartments abut shortens the boundary and reduces the intercalation of cells from different compartments.
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Further Reading

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Blair, Seth S(Jan 2017) Developmental Compartments. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026604]