Analyzing Mesenchyme Differentiation

To illustrate the use of gene-expression databases, we consider the example of the mesenchymal aggregates that form in mice. Mesenchyme is, it should be said, something of a catch-all word that describes apparently undifferentiated masses of cells in early embryos that mainly derive from mesoderm and will eventually form a wide range of tissues that includes bones, muscles, hair follicles, feathers, teeth, and nephrons. The first step in the formation of each is the aggregation of a group of mesenchymal cells to form a condensation (Fig. 1).  Understanding how these different tissues form from apparently very similar cells and condensations is a problem whose difficulty almost rivals that of the formation of the nervous system, but it is already clear that each requires a complex genetic pathway involving signals, receptors, transduction pathways, and tiers of transcription factors (for review, see Bard and Lehtonen 1996), as well as a wide range of morphogenetic mechanisms (Bard 1990).  Once the databases discussed here are in place, their integrated use will help elucidate the various developmental pathways in the following ways:

•  The anatomy database (DMDA) will provide a means of seeing when all these aggregates form (most, it turns out, appear at about E12-13). •  The text database (GXD) will detail those genes first expressed in early condensations and additional genes expressed as they differentiate. •  The graphical database (GGED) will give signaling and other genes expressed in the vicinity of condensations before they appear. •  The transgenic database (TBase) will give data on the function of genes expressed as aggregates differentiate. •  Interoperability will detail the behavior of homologous genes in other organisms.