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Fig. 5. Differential use of the retinal determination gene network (RDGN) in muscle
versus ear development. (A) A schematic of the vertebrate otic placode, which
can be identified at the 4- to 13-somite stage of mouse development, shown as
a cross-section through the developing embryo. HB, hindbrain; NC, notochord.
The placode invaginates at embryonic day 9 (E9) to form the otic vesicle,
which will close to form the otocyst. (B) The RDGN hierarchy in vertebrate
muscle development is analogous to that operating in the Drosophila
eye (see Fig. 1), with respect
to transcriptional regulation, protein-protein interactions and positive
feedback loops. However, the PAX protein that functions in muscle development
is PAX3, as opposed to PAX6, which functions in the eye. (C) The functions of
the RDGN during otic placode development are distinct from those operating in
the muscle. Most strikingly, DAC/DACH proteins appear to function in a
parallel pathway to Eyes absent (EYA)/SIX that is negatively regulated by
SIX1. Feedback loops in which downstream members influence the expression of
upstream components are also not apparent. Black arrows indicate
transcriptional regulation, either positive or negative. Broken black arrows
reflect the uncertainty in the positioning of PAX2 and PAX8 upstream of EYA2
and SIX1. Double-headed pink arrows indicate the synergistic interactions that
reflect possible direct protein-protein associations.
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