LIM Homeobox Genes and the CNS A Close Relationship

A Close Relationship protein interactions. LHX proteins have a conserved structure in which two distinct LIM domains are placed N-terminal of a centrally located DNA binding homeodomain, while the C-termi-Homeobox genes are the prototypical patterning fac-nal region contains activating, repressing, and possibly tors. There is hardly a patterning process, establishment other functional elements (second figure). The LIM do-of polarity, or determination of cellular identity during mains interact strongly with members of a small group metazoan development without the critical involvement of proteins named Ldb, NLI, Chip, or CLIM (reviewed in of this class of genes. Among the many homeodomain Ldb is a small protein with siderable interest for several reasons. One point is the no previously known structural motifs, which appears role of the LIM domain, a modified zinc finger domain, to function entirely as an adaptor in protein interactions. in protein–protein interactions. While homeodomains Its major known function is to mediate LHX protein di-themselves are known to interact with other proteins, merization by way of its LIM interacting domain (LID) conserved associated domains such as the POU domain and dimerization domain, as illustrated in the second are generally DNA rather than protein binding, giving figure. It has been shown that the LIM domains become the LIM domain a distinct character. Another point is dispensable for function of the Drosophila LHX protein the major, albeit not exclusive, focus of LIM homeobox Apterous if dimerization is promoted by covalently link-(LHX) gene function in patterning the CNS. In Caeno-ing the dimerization domain of Chip (Ldb) to an Apterous rhabditis elegans, where two of the three founding mem-sequence from which the LIM domains have been de-bers of the LHX family were discovered, this class of leted (Milan and Cohen, 1999; van Meyel et al., 1999). genes is almost exclusively involved in establishing neu-As the Ldb molecule can bind to all LIM domains from ronal identity and the pathways of axon tracts (reviewed LHX proteins (there are other types of LIM domains, and in Dawid et al. Ldb does not interact with them), it can mediate both Westphal, 2000; Bach, 2000). While many additional LHX protein homodimerization and heterodimerization. functions have been acquired by LHX genes in other Further, Ldb can interact with certain homeodomain pro-organisms such as Drosophila and vertebrates, a neural teins that lack LIM domains, allowing multiple potential bias in their expression and function remains. It has associations. In addition, the …