Editors' ChoiceDevelopmental Biology

Eye Sees Reciprocal Repression

Science's STKE  03 Oct 2000:
Vol. 2000, Issue 52, pp. tw10
DOI: 10.1126/stke.2000.52.tw10

How boundaries between adjacent tissues are defined during embryogenesis remains a major question in developmental biology. Schwarz et al. studied the role of the transcription factors Pax2 and Pax6 in defining the optic stalk and optic cup boundary in developing mice. Pax2 is involved in defining the optic stalk, and Pax6 is essential for eye development and defines the optic cup, including the retina and pigmented and lens epithelia. Pax2 knockout mice produce an eye in which the Pax6 regions have expanded and invaded the optic stalk; Pax6 knockout mice are eyeless. Expression of Pax6 under the control of the Pax2 promoter similarly converts the glial progenitors into retinal cells in the region of the optic stalk, suggesting that Pax6 can repress Pax2 activity. Sequence analysis and gel-shift assays with the Pax2 promoter and the Pax6 retina-specific enhancer region showed that Pax2 and Pax6 each binds to its own and each other's regulatory regions, suggesting reciprocal regulation. Reciprocal repression was confirmed by the use of reporter gene constructs with the Pax2 or Pax6 regulatory regions: Pax2 was found to repress activity of the Pax6 promoter, Pax6 enhanced Pax6 promoter activity, and Pax6 repressed activity of the Pax2 promoter. These data suggest a model by which Pax6 can give feedback to enhance its own synthesis and to repress Pax2 synthesis and Pax2 can repress Pax6 synthesis, leading to a sharp boundary at the optic stalk and cup junction.

Schwarz, M., Cecconi, F., Bernier, G., Andrejewski, N., Kammandel, B., Wagner, M., and Gruss, P. (2000) Spatial specification of mammalian eye territories by reciprocal transcriptional repression of Pax2 and Pax6. Development 127: 4325-4334. [Online Journal]