Abdominal-A mediated repression of Cyclin E expression during cell-fate specification in the Drosophila central nervous system

Abstract

Homeotic/Hox genes are known to specify a given developmental pathway by regulating the expression of downstream effector genes. During embryonic CNS development of Drosophila, the Hox protein Abdominal-A (AbdA) is required for the specification of the abdominal NB6-4 lineage. It does so by down regulating the expression of the cell cycle regulator gene Dcyclin E (CycE). CycE is normally expressed in the thoracic NB6-4 lineage to give rise to mixed lineage of neurons and glia, while only glial cells are produced from the abdominal NB6-4 lineage due to the repression of CycE by AbdA. Here we investigate how AbdA represses the expression of CycE to define the abdominal fate of a single NB6-4 precursor cell. We analyze, both in vitro and in vivo, the regulation of a 1.9 kb CNS-specific CycE enhancer element in the abdominal NB6-4 lineage. We show that CycE is a direct target of AbdA and it binds to the CNS specific enhancer of CycE to specifically repress the enhancer activity in vivo. Our results suggest preferential involvement of a series of multiple AbdA binding sites to selectively enhance the repression of CycE transcription. Furthermore, our data suggest a complex network to regulate CycE expression where AbdA functions as a key regulator.