p38 MAPK as an essential regulator of dorsal-ventral axis specification and skeletogenesis during sea urchin development: a re-evaluation [RESEARCH ARTICLE]

Maria Dolores Molina, Magali Quirin, Emmanuel Haillot, Felipe Jimenez, Aline Chessel, and Thierry Lepage

Dorsal-ventral axis formation in the sea urchin embryo relies on the asymmetrical expression of the TGF-beta Nodal. The p38-MAPK pathway has been proposed to be essential for dorsal-ventral axis formation by acting upstream of nodal expression. Herein, we report that, in contrast to previous studies that used pharmacological inhibitors of p38, manipulating the activity of p38 by genetic means has no obvious impact on morphogenesis. Instead, we discovered that p38 inhibitors strongly disrupt specification of all germ layers by blocking signalling from the Nodal receptor and by interfering with the ERK pathway. Strikingly, while expression of a p38 mutant resistant to SB203580 did not rescue dorsal-ventral axis formation or skeletogenesis in embryos treated with this inhibitor, expression of Nodal receptor mutants resistant to SB203580 fully restored nodal expression in SB203580 treated embryos. Taken together, these results establish that p38 activity is required neither for dorsal-ventral axis formation through nodal expression nor for skeletogenesis. Our results prompt a re-evaluation of the conclusions of several recent studies that linked p38 activity to dorsal-ventral axis formation and to patterning of the skeleton.

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