Development: DV patterning in time and AP space

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A study in zebrafish has revealed that protein concentration and temporal cues are important for bone morphogenetic protein (BMP)-mediated dorsoventral patterning during development.

Spatial differences in morphogen concentration instruct cells to adopt different developmental fates. Given the diffusible nature of morphogens, there is also a temporal pattern to a morphogen gradient. Whereas this pattern has clearly been established for the vertebrate anteroposterior (AP) axis, models of dorsoventral (DV) patterning have by and large been static. Working in zebrafish, Mullins and colleagues now reveal the temporal dynamics of bone morphogenetic protein (BMP) signalling that underlies DV patterning, and show how it is integrated with patterning along the AP axis.

The authors generated a zebrafish strain that was mutant for alk8, a BMP receptor, but that also carried a transgene with alk8 cDNA downstream of a heat-shock inducible promoter. Activation of BMP signalling in this way at precise times during early embryonic development revealed that cells begin to respond to BMP signalling at or just after gastrulation. But it is only the ventrolateral cranial and trunk tissues that are patterned at this time; the tail is patterned later in embryogenesis, at the early somite stage.

To better understand this temporal and spatial difference, the authors generated transgenic fish in which the cDNA of a BMP antagonist, chordin, was hooked up to a heat-shock promoter. This allowed complete, rapid and inducible BMP inhibition. Careful analysis of embryos in which BMP had been inhibited at different times revealed that the later this protein is inhibited, the less severe the dorsalizing effects are. Moreover, later inhibition affected more posterior parts of the body, confirming that the head and trunk are patterned during distinct periods.

The fact that DV patterning of more posterior structures takes place at a later embryonic stage might indicate that these structures require prolonged BMP signalling. By injecting bmp2b mRNA into transgenic embryos in which BMP had previously been inhibited and by turning BMP signalling on through alk8 receptor induction, the authors show that this is not the case — yet another piece of evidence for progressive DV patterning along the AP axis over time.

Collectively, these results indicate that "a temporal cue regulates a cell's competence to respond to BMP, allowing the acquisition of a cell's DV and AP identity simultaneously." This work also shows that BMP is different from other morphogens in an important way — in contrast to BMP, their ability to specify different cell identities involves not only varying concentration levels but also the duration of exposure to the signal.

Magdalena Skipper

References

Tucker, J. A. et al. The BMP signaling gradient patterns dorsoventral tissues in a temporally progressive manner along the anteroposterior axis. Dev. Cell 14, 108–119 (2008) | Article | PubMed |
Affolter, M. & Basler, K. The decapentaplegic morphogen gradient: from pattern formation to growth regulation. Nature Rev. Genet. 8, 663–674 (2007) | Article | PubMed |