A. Grapin-botton et al., Patterning signals acting in the spinal cord override the organizing activity of the isthmus, MECH DEVEL, 84(1-2), 1999, pp. 41-53
The regionalization of the neural tube along the anteroposterior axis is es
tablished through the action of patterning signals from the endo-mesoderm i
ncluding the organizer. These signals set up a pre-pattern which is subsequ
ently refined through local patterning events. The midbrain-hindbrain junct
ion, or isthmus, is endowed with such an organizing activity. It is able to
induce graded expression of the Engrailed protein in the adjacent mesencep
halon and rhombencephalon, and subsequently elicits the development of rect
al and cerebellar structures. Ectopically grafted isthmus was also shown to
induce Engrailed expression in diencephalon and otic and pre-otic rhombenc
ephalon. Fgf8 is a signalling protein which is produced by the isthmus and
which is able to mimic most isthmic properties. We show here that the isthm
us, when transposed to the level of either rhombomere 8 or the spinal cord,
loses its ability to induce Engrailed and cerebellar development in adjace
nt tissues. This is accompanied by the down-regulation of fgf8 expression i
n the grafted isthmus and by the up-regulation of a marker of the recipient
site, Hoxb-4. Moreover, these changes in gene activity in the transplant a
re followed by a transformation of the fate of the grafted cells which adju
st to their novel environment. These results show that the Tale of the isth
mus is not determined at 10-somite stage and that the molecular loop of ist
hmic maintenance can be disrupted by exogenous signals. (C) 1999 Elsevier S
cience Ireland Ltd. All rights reserved.