Asymmetric cell division: fateful FGF antagonism

Asymmetric cell division during embryogenesis contributes to cell diversity by generating daughter cells that adopt distinct developmental fates. Little is known about how many of these asymmetric divisions are regulated, but two papers in this issue suggest that FGF signalling plus an ectoderm-derived signal control asymmetric division and the specification of notochord/neural precursors in ascidian embryos. In these embryos, two pairs of mother cells give rise to neural and notochord precursors. Daughter cells in which ERK is activated develop into notochord cells, whereas the others develop into neural cells. But FGF and its receptor, which activate ERK, are widely distributed in the mother cells and surrounding vegetal cells, so how is an asymmetric cue generated? On p. 1491,Picco and colleagues show that the segregation of notochord and neural fates in Ciona embryos is an intrinsic property of the mother cells that is acquired through their interaction with ectoderm precursors. This interaction is mediated by the ephrin-Eph signalling system, which is better known for its roles in axon guidance and cell adhesion. The inhibition of ephrin-Eph signalling causes symmetric cell division and generates only notochord precursors, the researchers report. The ephrin-Eph signal attenuates ERK activation in the neural-fated daughter cell. Thus, a directional ephrin-Eph signal from the ectoderm polarises the notochord/neural mother cell and asymmetrically modulates ERK activation and fate specification in the daughter cells. On p. 1509, Kim and colleagues examine the specification of notochord/neural precursors and of mesenchyme/muscle precursors in another ascidian, Halocynthia roretzi. They find that a directional FGF signal alone determines the asymmetric division of the muscle/mesenchyme mother cells, but that an FGF antagonising signal from the neighbouring ectoderm controls the polarity of the notochord/neural mother cells. This signal suppresses FGF signal transduction in the neural-fated daughter cell and the expression of FoxA, which encodes an essential transcription factor for notochord formation. Together, these two papers provide strong evidence for a new mechanism by which FGF signalling, in combination with an antagonising signal from the ectoderm, controls asymmetric cell division and cell fate specification during ascidian notochord/neural development.