Effects of Wnt1 signaling on proliferation in the developing mid-/hindbrain region.

The secreted glycoprotein WNT1 is expressed in the caudal midbrain and is essential for proper development of the entire mid-/hindbrain region. To get better insights into Wnt1 function in the mid-/hindbrain region, we ectopically expressed Wnt1 under the control of the endogenous En1 promoter, thereby extending Wnt1 expression rostrally into the anterior midbrain and caudally into rhombomere 1. In these transgenic mice, the position of the mid-/hindbrain organizer is not altered and pattern formation is not changed. During midgestation, ectopic Wnt1 induced strong overproliferation of precursor cells only in the caudal midbrain in a gene dosage-dependent manner. Enhanced proliferation is at least in part mediated by shortening of the cell cycle length. In adults, Wnt1 exhibited a cell size promoting effect specifically on neurons. We suggest that Wnt1 acts as a regulator of proliferation of specific precursor populations in the developing mid-/hindbrain region and is only secondarily involved in maintenance of the mid-/hindbrain organizer.