REGULATION OF DESMOCOLLIN TRANSCRIPTION IN MOUSE PREIMPLANTATION EMBRYOS

The molecular mechanisms regulating the biogenesis of the first desmos omes to form during mouse embryogenesis have been studied. A sensitive modification of a reverse transcriptase - cDNA amplification procedur e has been used to detect transcripts of the desmosomal adhesive cadhe rin, desmocollin. Sequencing of cDNA amplification products confirmed that two splice variants, a and b, of the DSC2 gene are transcribed co ordinately. Transcripts were identified in unfertilized eggs and cumul us cells and in cleavage stages up to the early 8-cell stage, were nev er detected in compact 8-cell embryos, but were evident again either f rom the 16-cell morula or very early blastocyst (approx 32-cells) stag es onwards. These two phases of transcript detection indicate DSC2 is encoded by maternal and embryonic genomes. Previously, we have shown t hat desmocollin protein synthesis is undetectable in eggs and cleavage stages but initiates at the early blastocyst stage when desmocollin l ocalises at, and appears to regulate assembly of, nascent desmosomes t hat form in the trophectoderm but not in the inner cell mass (Fleming, T. P., Garrod, D. R. and Elsmore, A. J. (1991), Development 112, 527- 539). Maternal DSC2 mRNA is therefore not translated and presumably is inherited by blastomeres before complete degradation. Our results sug gest, however, that initiation of embryonic DSC2 transcription regulat es desmocollin protein expression and thereby desmosome formation. Mor eover, data from blastocyst single cell analyses suggest that embryoni c DSC2 transcription is specific to the trophectoderm lineage. Inhibit ion of E-cadherin-mediated cell-cell adhesion did not influence the ti ming of DSC2 embryonic transcription and protein expression. However, isolation and culture of inner cell masses induced an increase in the amount of DSC2 mRNA and protein detected. Taken together, these result s suggest that the presence of a contact-free cell surface activates D SC2 transcription in the mouse early embryo.