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First published online 26 October 2005
doi: 10.1242/dev.02100
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1 Department of Genetics and Howard Hughes Medical Institute, Harvard Medical
School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
2 Department of Biology, Oberlin College, 119 Woodland Street, Oberlin, OH
44074-1097, USA
* Author for correspondence (email: cepko{at}genetics.med.harvard.edu)
Accepted 22 September 2005
Asymmetric expression of several genes in the early eye anlagen is required
for the dorsoventral (DV) and anteroposterior (AP) patterning of the retina.
Some of these early patterning genes play a role in determining the graded
expression of molecules that are needed to form the retinotectal map. The
polarized expression of retinoic acid synthesizing and degrading enzymes along
the DV axis in the retina leads to several zones of varied retinoic acid (RA)
activity. This is suggestive of RA playing a role in DV patterning of the
retina. A dominant-negative form of the retinoic acid receptor 
(DNhRAR) was expressed in the chick retina to block RA activity. RA
signaling was found to play a role in regulating the expression of EphB2,
EphB3 and ephrin B2, three molecules whose graded expression in the retina
along the DV axis is important for establishing the correct retinotectal map.
Blocking RA signaling by misexpression of a RA degrading enzyme, Cyp26A1
recapitulated some but not all the effects of DNhRAR. It also was found
that Vax, a ventrally expressed transcription factor that regulates the
expression of the EphB and ephrin B molecules, functions upstream of, or in
parallel to, RA. Expression of DNhRAR led to increased levels of
RA-synthesizing enzymes and loss of RA-degrading enzymes. Activation of such
compensatory mechanisms when RA activity is blocked suggests that RA
homeostasis is very strictly regulated in the retina.
Key words: Retinoic acid, Dorsoventral, EphB, Ephrin B, Patterning, Retinotectal map
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