Stage, tissue, and cell specific distribution of alternative Ultrabithorax mRNAs and protein isoforms in the...

The homeotic gene Ultrabithorax encodes a family of six homeoproteins translated from alternatively spliced mRNAs. The structures of these UBX isoforms have been conserved among anciently diverged Drosoph-ila species and functional distinctions between some isoforms have been reported that suggest subtle but important roles in Ubx action. We present a detailed analysis of the expression patterns of Ubx mRNAs and proteins during embryogenesis, using isoform-specific monoclonal antibodies and synthetic oligonucleotide probes. These patterns are remarkably complex, each mRNA and corresponding protein isoform being expressed in a partially overlapping but distinct stage and tissue-specific pattern. The complexity is greatest in the central nervous system, where different isoforms predominate during successive developmental stages and where their relative proportions differ from one metamere to another and even among individual neurons within a given metamere. The distributions of UBX isoforms are consistent with those functional distinctions that have been described; they also suggest that different isoforms may be specialized or optimized to control different aspects of central nervous system development. The close correspondence between the mRNA and protein patterns indicates that the mRNAs do not differ strongly in translatability, despite the abundance of rare codons in the optional exons. There is a delay between the detection of particular splicing events in the nucleus and the detection of the 3' end of the message or the appearance of the corresponding mRNAs and proteins in the cytoplasm. This delay is consistent with the size of the Ubx introns and indicates a cotranscriptional mechanism of splicing.