Worm Breeder's Gazette 15(5): 29 (February 1, 1999)
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.
|1||IBDM, Luminy Case 907, 13288 Marseille Cedex 9, France|
|2||CIML, Luminy Case 906, 13288 Marseille Cedex 9, France|
We are studying a C. elegans homologue of a couple of vertebrate neuronal type-specific transcription factors of the prd-like homeobox gene superfamily, Phox2a and Phox2b (1,2,3). The predicted amino acid sequence of CePHOX2, also designated CEH-42 (4) and now renamed CEH-17 (5) is 88% identical to murine Phox2 proteins within the homeodomain, a level of similarity often associated with functional conservation between homeobox genes of vertebrates and invertebrates. Transgenic lines harboring gfp under the control of 1 kb of sequences upstream of CePhox2/ceh-17 reveal an expression largely restricted to a few neurons, mostly in the head. Among those, five are substantiated by immunohistochemistry with an antibody raised against the C-terminus of the predicted protein: ALA and 4 ventral neurons tentatively identified as SIB. Other neurons in the head, although they are also detected with a ceh-17/gfp fusion construct containing the two short introns of the gene are not detectable with the anti-CEH-17 antibody, raising the possibility that they correspond to ectopic expression sites.
We have generated a library of about 350 000 genomes mutagenized
with TMP/UV and isolated a target-selected mutation in CePhox2/ceh-17.
The allele ceh-17(np1) corresponds to a 1.3 kb deletion
extending from 0.6 kb upstram of the transcription start site
to the first helix of the homeodomain and is thus expected to
be a null. The homozygous mutants are viable. Crosses between
the mutant strain and an integrated pceh-17/gfp strain
allowed the detection of numerous axonal pathfinding defects.
In particular, the posteriorly directed growth of the two ALA
axons in the lateral cords is severely disrupted. Future work
is aimed at better characterizing the role of CePhox2/ceh-17
in axonal navigation in these loss-of-function as well as in yet-to-be-generated
gain-of-function mutants and assessing the orthology of ceh-17
and murine Phox2 by functional rescue.
Thanks to: Remi Terranova and Gary Moulder.
(1) Pattyn et al. (1997) Development, 124, 4065-4075, (2) Morin et al. (1997) Neuron, 18, 411-423 , (3) Ewbank et al. (1998) WBG 15 (3):17, (4) Hobert and Ruvkun (1998) ECWM98 (67), (5) Thomas Burglin, personal communication