The Gene Regulatory Network of Lens Induction Is Wired through Meis-Dependent Shadow Enhancers of Pax6
(A-E) At E12.5, external eyes of whole-mount Meis1-/-, Le-Cre;Meis2f/f, Le-Cre;Meis1+/-;Meis2f/f mutant appear comparable to control eye, whereas the eye of Le-Cre;Meis1-/-;Meis2f/f double mutant has abnormal shape. The insets show high magnification of eye region (boxed). (F-O) Hematoxylin-eosin stained parrafin sections show histology of control or mutant E10.5 and E12.5 eyes. (F-H, K-M) Formation of lens placode is followed by invagination of surface ectodem, formation of lens pit (LPi) and subsequent formation of lens in control, Meis1-/- and Le-Cre;Meis2f/f embryos. (I, N) One active Meis1 allele in Le-Cre;Meis1-/+; Meis2f/f embryos is sufficient for lens placode and lens formation. (J, O) In Le-Cre;Meis1-/-;Meis2f/f embryos, deficient for both Meis1 and Meis2, lens development is arrested in pre-placodal stage (arrowheads). * Artefact, le-lens, nr-neural retina.