EXPRESSION OF THE ZINC-FINGER GENE PLZF AT RHOMBOMERE BOUNDARIES IN THE VERTEBRATE HINDBRAIN

To investigate the potential biological role(s) of the PLZF gene, disc overed as a fusion with the RARA Locus in a patient with acute promyel ocytic leukemia harboring a t(11;17) chromosomal translocation, we hav e isolated its murine homologue (mPLZF) and studied its patterns of de velopmental expression. The levels of mPLZF mRNAs increased perinatall y in the liver, heart, and kidney, but with the exception of the heart , they were either absent or very low in the adult tissues. In situ an alysis of mPLZF expression in mouse embryos between 7.0 and 10.5 days of development revealed that mPLZF mRNAs and proteins were coexpressed in spatially restricted and temporally dynamic patterns in the centra l nervous system. In the hindbrain region, a segmental pattern of expr ession correlated with the development of the rhombomeres. From 9.0 da ys of development, starting first in rhombomeres 3 and 5, there was an ordered down-regulation of expression in the center of each rhombomer e, so that 1 day later elevated levels of mPLZF mRNAs and proteins wer e restricted to cells surrounding the rhombomeric boundaries. The chic ken homologue of the PLZF gene, which we have also cloned, demonstrate d a similar segmental pattern of expression in the hindbrain. To date, PLZF represents the only example of a transcription factor with eleva ted expression at rhombomeric boundaries. The high degree of evolution ary conservation between the patterns of PLZF expression during mammal ian and avian central nervous system development suggests that it has an important functional role in the regionalization of the vertebrate hindbrain, potentially regulating boundary cell interactions.