Worm Breeder's Gazette 17(1): 63 (October 1, 2001)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
|2||IBDM, Marseille, France|
|3||Karolinska Institutet, Huddinge, Sweden|
The Cut homeobox gene in Drosophila is required for the specification of neuronal identity in the external sensory organs of the peripheral nervous system. It is also involved in dorsoventral patterning of the wing margin and the formation of Malpighian tubule, tracheal system and some structure in the central nervous system. Two murine homologues of Cut, named Cux-1 and Cux-2 have been cloned. While Cux-1 is expressed in most tissue during development, Cux-2 expression is restricted to the nervous system. Interestingly, ectopic expression of Cux-1 in the fly was shown to rescue the wing scalloping phenotype in a cut mutant. This suggests at least partial conservation of Cut function between invertebrates and mammals (review 1).
The sequencing of the C. elegans genome has recently revealed the presence of a Cut-like gene, Y54F10AM.4a, which we call ceh-44. Several Y. Kohara cDNAs confirm the existence of a ceh-44 transcript. It has the same structure as other members of the Cut gene family, consisting of three cut repeats upstream of a cut class homeodomain. Phylogenetic analysis shows that the three cut repeats of CEH-44 are the most divergent of the Cux family, but still cluster with the Cut family. The three cut repeats are 45% (69%), 62% (79%) and 35% (52%) identical (similar) to Drosophila Cut, respectively. The homeodomain of CEH-44 is more divergent and does not cluster significantly with any family, being only 39% identical with mouse Cux-2. The gene is predicted to be the second in an operon downstream of Y54F10AM.5, which has sequence similarity with a NADH-ubiquinone oxidoreductase.
Several Y. Kohara cDNAs reveal a spliced form containing the 5' end of the ceh-44 gene, without the cut repeats and the homeodomain (the predicted Y54F10AM.4b form), linked to the predicted adjacent 3' gene Y54F10AM.3. This transcript encodes a protein similar to the vertebrate CASP proteins, the N-terminal part being shared with the vertebrate Cux proteins and CEH-44 (but not Drosophila Cut, which seems to have lost CASP). In the mouse, this protein also arises from alternative splicing of the Cux-1 transcript (2). However, the CASP protein is an evolutionarily old protein, also found in plants and fungi, where it is not associated with an homeobox gene. Thus CASP and an ancestral Cut gene must have merged in early animal evolution.
In situ experiments in Y. Kohara's database with yk394a11 (3), one of the cDNA corresponding to ceh-44, reveal an early embryonic expression, mostly anterior in the coma stage, as well as in the nerve ring in the larvae and in the gonad in the adult. Our future aim will be to test if ceh-44 in C. elegans functions as a determinant of cell-type specification comparable to Cut in the fly. We will study in more details the ceh-44 expression pattern with GFP fusions and plan to perform loss-of-function and gain-of-function studies.
1. Nepveu A. Gene 2001 2. Lievens P. et al. Gene 1997.