Patterning signals acting in the spinal cord override the organizing activity of the isthmus

Citation
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
Citations number
55
Categorie Soggetti
Cell & Developmental Biology
Journal title
MECHANISMS OF DEVELOPMENT
ISSN journal
09254773 → ACNP
Volume
84
Issue
1-2
Year of publication
1999
Pages
41 - 53
Database
ISI
SICI code
0925-4773(199906)84:1-2<41:PSAITS>2.0.ZU;2-S
Abstract
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.