Vertical regulation of En-2 expression and eye development by FGFs and BMPs

The formation of the midbrain region depends mainly on the activity of a si gnalling center located in the isthmus region, on the border between the pr ospective mesencephalon and metencephalon. FGF-8 has been proposed as a sig nalling molecule responsible for this specification because of its expressi on pattern and its ability to elicit duplication of the midbrain region whe n expressed ectopically in the neuroepithelium. Here we present evidence th at members of the FGF family of growth factors when released in the cephali c mesenchyme are able to extend the expression of the mesencephalic marker En-2 to both the anterior and the posterior regions of its original landmar k. This alteration in the expression pattern of En-2 is not accompanied by a significant alteration in the later development of the midbrain-cerebella r anlage. although the eye development is severely altered. Members of the bone morphogenetic protein family ectopically released from the mesenchyme down-regulate the expression of En-2 and also have an effect on the develop ment of the eye. These results demonstrate that growth factor molecules pro duced in the mesenchyme (vertical signalling) participate in the correct es tablishment of the antero-posterior patterning of the cephalic nervous syst em during development.