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Evolutionarily conserved developmental pathways

Cell polarity - a conserved role for CDC42 and PAR proteins

Generation of asymmetry in the one-cell embryo of C. elegans establishes theanterior-posterior axis (A-P), and is necessary for the proper identity of early blastomeres. Conserved PAR proteins are asymmetrically distributed and are required for the generation of this early asymmetry. The small G protein Cdc42 (see Drosophila Cdc42)is a key regulator of polarity in other systems, and recently it has been shown to interact with the mammalian homolog of PAR-6 (see Drosophila par-6). The function of Cdc42 in C. eleganshad not yet been investigated, however. C. elegans cdc-42 plays an essential role in the polarity of the one-cell embryo and the proper localization of PAR proteins. Inhibition of cdc-42 using RNA interference results in embryos with a phenotype that is nearly identical to par-3, par-6, and pkc-3 mutants, and asymmetric localization of these and other PAR proteins is lost. CDC-42 physically interacts with PAR-6 in a yeast two-hybrid system, consistent with data on the interaction of human homologs. It is concluded that CDC-42 acts in concert with the PAR proteins to control the polarity of the C. elegans embryo, and the interaction of CDC-42 and the PAR-3/PAR-6/PKC-3 complex has been evolutionarily conserved as a functional unit (Gotta, 2001).

Drosophila gene bazooka codes for a protein implicated in the formation of the cell-cell junction called the zonula adherins. This protein is a homolog of C. elegans Par-3. The multi-PDZ domain protein Bazooka (Baz) is required for establishment of apico-basal polarity in epithelia and in neuroblasts, the stem cells of the central nervous system. In neuroblasts, Baz anchors Inscuteable in the apical cytocortex, which is essential for asymmetric localization of cell fate determinants and for proper orientation of the mitotic spindle. Baz directly binds to the Drosophila Atypical protein kinase C (aPKC), the homolog of C. elegans Pkc-3, and both proteins are mutually dependent on each other for correct apical localization. Loss-of-function mutants of the Drosophila aPKC show loss of apico-basal polarity, multilayering of epithelia, mislocalization of Inscuteable and abnormal spindle orientation in neuroblasts. Together, these data provide strong evidence for the existence of an evolutionary conserved mechanism that controls apico-basal polarity in epithelia and neuronal stem cells (Wodarz, 2000).

date revised: 25 April 2001

Developmental Pathways conserved in Evolution

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