MATH-2, A MAMMALIAN HELIX-LOOP-HELIX FACTOR STRUCTURALLY RELATED TO THE PRODUCT OF DROSOPHILA PRONEURAL GENE ATONAL, IS SPECIFICALLY EXPRESSED IN THE NERVOUS-SYSTEM

In Drosophila, multiple helix-loop-helix (HLH) factors play an essenti al role in neural development. Mammalian homologues of such Drosophila HLH factors have been recently characterized and provide useful infor mation for the analysis of the mechanisms of mammalian neurogenesis. W e report here the molecular characterization of a novel mouse HLH fact or, designated MATH-2, that has a structural homology to the product o f Drosophila proneural gene atonal. MATH-2 consists of 337 amino acid residues and contains an atonal-related basic HLH domain. However, out side of this domain, there is no significant sequence similarity betwe en MATH-2 and Atonal. MATH-2 expression occurs by embryonic day 11.5 ( E11.5), and is first detected in the wall of brain vesicles as well as in the spinal cord. It is expressed in the cortical plate and the man tle layer throughout the developing central nervous system but not in the ventricular zone. By E13.5, the expression becomes more prominent in the cortical plate of the cerebrum but decreases in the other regio ns. In the adult, the cerebrum produces a high level of MATH-2 RNA but other neural tissues produce only low levels. MATH-2 RNA is not detec ted in non-neural tissues, indicating that MATH-2 expression is specif ic to the nervous system. The gel mobility-shift analysis shows that M ATH-2 can interact with several E-box sequences in collaboration with E47, a ubiquitously expressed HLH factor. These results raise the poss ibility that MATH-2 may be a trans-acting factor involved in the devel opment and maintenance of the mammalian nervous system.