Bilateral symmetry of an animal''s body plan is one of unique feature of higher animals. The nervous system is largely bilaterally symmetric on a morphological level, but often displays striking degrees of functional left/right asymmetry. For example, human patients with inversus totalis show reversal of visceral asymmetries, but functional asymmetries of the brain, such as language dominance, remain intact in these patients. It therefore remains unclear how functional asymmetries of morphologically bilaterally symmetric structures are established within the nervous system and how they relate to visceral asymmetries. Given how little is understood about cell fate specification after the beginning of gastrulation, and how left-right asymmetries are generated, the homeobox gene
ceh-5 provides a very interesting entry point. Homeobox genes are transcription factors that play key roles in the development of human and animals, and are highly conserved in evolution.
ceh-5, ortholog to the human VAX genes, shows a unique expression pattern during early embryogenesis of C. elegans. It is strongly expressed in two distinct groups of cells, one laterally and one at the very anterior that are separated both in space and time, and later become neurons. Further, a third group of cells is expressing
ceh-5 at a very low level, and this group appears to be mirror-symmetrical to the first, laterally expressed group. Therefore, we believe that
ceh-5 displays left/right asymmetry in this pattern. The major aim of this project is to use the expression pattern of
ceh-5 as a marker to study how asymmetric gene expression is established during early neurogenesis. For this we are currently analysing the promoter region of
ceh-5 by creating reporter constructs with different parts of the promoter region of
ceh-5 fused to the green fluorescent protein, and subsequently generating transgenic animals carrying these promoter constructs. The transgenic animals will be examined to determine in which parts of the embryo the constructs are expressed and in which way the expression deviates from the expression of a full length
ceh-5::GFP construct.