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Abstract:
Based on mutants isolated in large scale screens, Bmp2b and Bmp7, their type I receptor Alk8, the downstream transcription factor Smad5, and the secreted Bmp antagonist Chordin were identified as essential components regulating zebrafish D-V patterning. Analyses of mutant embryos suggest that D-V patterning occurs in three distinct phases. During the first two phases a D-V gradient of Bmp activity is set up, which in the third phase leads to differential cell fate specifications along the D-V axis.
Using a substractive approach, we identified DNp63, a member of the p53/63/73 family of tumor suppressors, as a direct transcriptional target of Bmp2b/7 signaling. DNp63 acts as a transcriptional repressor, mediating the effect of Bmp signaling during dorsoventral patterning of the ectoderm to block neural development in the presumptive epidermal ectoderm. Comparing this early role with the later role of DNp63 to promote the maintenance of skin stem cells, we suggest that Bmps and DNp63 have a similar, specification-blocking function in the non-neural ectoderm of the gastrulating embryo.
In addition to cell fate determination, Bmps have been shown to regulate differential cell movement behavior along the D-V axis. Here, we dissect the two roles, showing that Hyaluronan synthase 2 (Has2) interacts with Bmps during cell movements, but not during dorsoventral patterning. Loss of Has2 function leads to a block of dorsal convergence as in bmp mutants, however, in contrast to bmp mutants, has2 morphants are not dorsalized. In contrast to DNp63, Has2 does not act downstream of Bmps. Rather, Has2 and Bmps act in parallel, with Has2 regulating the migratory potential of cells, and Bmps determining the direction of the migration.
