Forming patterns in development without morphogen gradients: scattered differentiation and sorting out

Abstract

Few mechanisms provide alternatives to morphogen gradients for producing spatial patterns of cells in development. One possibility is based on the sorting out of cells that initially differentiate in a salt and pepper mixture and then physically move to create coherent tissues. Here, we describe the evidence suggesting this is the major mode of patterning in Dictyostelium. In addition, we discuss whether convergent evolution could have produced a conceptually similar mechanism in other organisms.

Figure 1.

Alternative ways of patterning cells during development. (A) Patterning by “positional information”: A group of undifferentiated cells is patterned by a morphogen diffusing from a pre-established source, producing a concentration gradient. Cells respond according to the local morphogen concentration, becoming red, white, or blue. (B, C) Patterning without positional information: This is a two-step process in which different cell types first differentiate mixed up with each other, and then sort out. The initial differentiation can be controlled by strictly local interactions between the cells, as in lateral inhibition (B), or by a global signal to which cells respond with different sensitivities and whose concentration they regulate by negative feedback (C). Once sorting has occurred, the global inducer forms a reverse gradient, which could then convey positional information for further patterning events.

Figure 2.

Patterning in Dictyostelium development. (A) Schematic representation of the organization of different cell types at the slug stage. Prestalk-A cells are shown in white, prestalk-O in green, prestalk-AB and prestalk-B in blue, and prespore in red. (B) Pattern in the slug revealed by in situ hybridization to prestalk and prespore specific mRNAs. Left hand panel shows the overall organization of the slug, as revealed using probes to a prespore (red, probe from pspA) and a generic prestalk mRNA (green, probe from ecmB); the right hand panel shows the subdivision of the prestalk region into prestalk-O cells (green; probe from SSM184 cDNA) and prestalk-A cells (unstained). The front of the slug is to the right in both cases. Images courtesy Mineko Maeda and Yoko Yamada (see Yamada et al. 2005). (C) Sorting out of prestalk cells. Prestalk cells, marked by ecmAO-lacZ, are first detected at the mound stage of development, intermingled with unstained (prespore) cells. They subsequently sort out to form a distinct prestalk zone at the top of the mound, which then elongates to form a standing slug with the prestalk cells at the front. (D) Regulation of the proportion of prestalk-O cells. These cells are induced by a diffusible polyketide called DIF-1, which they inactivate by dechlorination. DIF-1 is produced by prespore cells, but inhibits their differentiation. Thus, DIF-1 levels and the proportion of prestalk-O cells are regulated by two negative feedback loops.

Figure 3.

Fate mapping the apical ectodermal ridge (AER) of the chick limb bud. A small group of cells is stained with fluorescent dye, and then followed into the AER. (A) Initial staining. (B) The resulting staining: Both the AER (a fluorescent line at the edge of the hemispherical limb bud) and scattered fluorescent cells are stained. (C) Intermingling of stained and unstained cells at higher power. (D) The fate map is shown in the lower panel. AER cells are recruited from a wide area, and the initial stained cells can: (closed circles) not contribute to the ridge; or (open circles) only contribute to the ridge; (circles with dots) contribute both to the ridge and other tissues. The fate map therefore has intermingled ridge and nonridge cells. (Modified, with permission, from Altabef et al. 1997 [©Company of Biologists].)