The developing nervous system's morphology is crucial for establishing functional circuits. The Joyner lab previously showed that engrailed 1(En1) mouse mutants lack most of the tectum and cerebellum (Cb) and die at birth, whereas En2 mutants survive but have smaller cerebellums; the earlier expression of En1, rather than differences in protein function, account for these differences. This group now report that En proteins mediate a dosage-dependent genetic subdivision of the tectum into its two functional systems and the cerebellum into six distinct regions (see ). The posterior tectum is reduced when En1 is conditionally deleted before E9; however, two copies of En2 can sustain Cb development in these mice. A functional comparison of Drosophila engrailed, En1 and En2 indicates that En2, but not engrailed can rescue En1 mouse mutant brain defects in the absence of endogenous En2. Interestingly, En1/2 double mutants have neural phenotypes similar to those of Fgf mutants, indicating that En1/2 either maintains Fgf expression or acts downstream of it.
