Analysis of Biological Development (K. Kalthoff)

Updates to Topic 22E: Compartment Hypothesis and Appendage Formation

New Review Articles

Dahmann C. and K. Basler (1999) Compartment boundaries. Trends Genet. 15: 320-326

Milán M. and S. Cohen (2000) Subdividing cell populations in the developing limbs of Drosophila: Do wing veins and leg segments define units of growth control? Devel. Biol. 217: 1-9

New Research Articles

Bruckner K., Perez L., Clausen H. and Cohen S. (2000) Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature 406: 411-415

Moloney D.J., Panin V.M., Johnston S.H., Chen J., Shao L., Wilson R., Wang Y., Stanley P., Irvine K.D., Haltiwanger R.S. and Vogt T. (2000) Fringe is a glycosyltransferase that modifies Notch. Nature 406: 369-375

Notch receptors and their ligands are broadly expressed in animal development, but their activity can be positively or negatively modulated to allow formation of tissue boundaries, e.g. along the dorsoventral boundary of the developing Drosophila wing imaginal disc (see p.596 of textbook). Members of the Fringe protein family have been implicated in limiting Notch activation during boundary formation, but the mechanism of Fringe function was unknown. These two studies present evidence that Fringe acts in the Golgi as a glycosyltransferase enzyme that initiates elongation of O-linked fucose residues attached to EGF-like sequence repeats of Notch, thereby altering the ability of Notch to bind its ligand Delta. Fringe does not alter the ability of Notch to bind Delta when provided as an extracellular protein but does act when co-expressed with Notch by the same cell. The post-translational modification of Notch by Fringe represents a striking example of modulation of a signalling event by differential receptor glycosylation and identifies a mechanism that may be relevant to other signalling pathways.

Casares F, Mann RS. (2001) The ground state of the ventral appendage in Drosophila. Science 293: 1477-1480

In Drosophila melanogaster, the antennae, legs, genitalia, and analia make up a serially homologous set of ventral appendages that depend on different selector genes for their unique identities. The diversity among these structures implies that there is a common ground state that selector genes modify to generate these different appendage morphologies. The investigators show that the ventral appendage that forms in the absence of selector gene activity is leglike but consists of only two segments along its proximo-distal axis: a proximal segment and a distal tarsus.

Dahmann C. and Basler K. (2000) Opposing transcriptional outputs of Hedgehog signaling and engrailed control compartmental cell sorting at the Drosophila A/P boundary. Cell 100: 411-422

The wing imaginal disc is subdivided into two nonintermingling sets of cells, the anterior (A) and posterior (P) compartments. Anterior cells require reception of the Hedgehog (Hh) signal to segregate from P cells. The investigators show that Hh signaling controls A/P cell segregation by a Cubitus interruptus (Ci)-mediated transcriptional response. A shift in the balance between repressor and activator forms of Ci toward the activator form is necessary and sufficient to define "A-type" cell sorting behavior. In the absence of Ci, Engrailed (En) is sufficient to specify "P-type" sorting. The authors propose that the opposing transcriptional activities of Ci and En control cell segregation at the A/P boundary by regulating a single cell adhesion molecule.

Dong P.D., Chu J. and Panganiban G. (2001) Proximodistal domain specification and interactions in developing Drosophila appendages. Development 128: 2365-2372

The arthropod antenna and leg are homologous appendages, thought to have arisen via duplication and divergence of an ancestral structure. To gain insight into how variations between the antenna and the leg may have arisen, the investigators compared the epistatic relationships among three major proximodistal patterning genes, Distal-less+, dachshund+, and homothorax+, in the antenna and leg of Drosophila melanogaster. We find that Drosophila appendages are subdivided into different proximodistal domains specified by specific genes, and that limb-specific interactions between genes and the functions of these genes are crucial for antenna-leg differences. In particular, in the leg, but not in the antenna, mutually antagonistic interactions exist between the proximal and medial domains, as well as between medial and distal domains. The lack of such antagonism in the antenna leads to extensive coexpression of Distal-less+ and homothorax+, which in turn is essential for differentiation of antennal morphology. Furthermore, we report that a fundamental difference between the two appendages is the presence in the leg and absence in the antenna of a functional medial domain specified by dachshund+. The authors propose that the acquisition of particular proximodistal subdomains and the evolution of their interactions has been essential for the diversification of limb morphology.

Milan M. and , Cohen S.M. (2000) Temporal regulation of apterous activity during development of the Drosophila wing. Development 127: 3069-3078

Dorsoventral axis formation in the Drosophila wing depends on the activity of the selector gene apterous. Apterous activity confers dorsal fate and induces the expression of Serrate, a Notch ligand. Notch then induces adjacent ventral cells to synthesize Wingless and Delta, another Notch ligand. Apterous also directs dorsal cells to produce Fringe, a glycosyltransferase that makes Notch expressed in the same cell more sensitive to Delta and refractory to Serrate [see Bruckner et al. (2000) and Moloney et al. (2000), above]. This limits the activity of Notch and the synthesis of Wingless to cells in close proximity to the dorsoventral boundary (see Fig. 22.51 of text). The ability of cells to participate in this Apterous-dependent cell-interaction is under spatial and temporal control. Apterous-dependent expression of its target gene dLMO causes downregulation of Serrate and fringe and allows expression of delta in dorsal cells. This limits the time window during which dorsoventral cell interactions can lead to localized activation of Notch and induction of the dorsoventral organizer. Overactivation of Apterous in the absence of dLMO leads to overexpression of Serrate, reduced expression of delta and concomitant defects in differentiation and cell survival in the wing primordium. Thus, downregulation of Apterous activity is needed to allow normal wing development.

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