Worm Breeder's Gazette 15(3): 17 (June 1, 1998)

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.

600 million years of Phox2.

Jonathan Ewbank1, Alexandre Pattyn2, Jean-Francois Brunet2

1 CIML, Luminy Case 906, 13288 Marseille Cedex 9, France
2 IBDM, Luminy Case 907, 13288 Marseille Cedex 9, France

We are studying a C. elegans homologue of a couple of vertebrate 
neuron-specific transcription factors, to explore phylogenetic aspects 
of neuronal identity and of its transcriptional determination. Phox2a
and  Phox2b are two closely related homeodomain proteins of the
paired-like  family specifically expressed (mostly co-expressed) in
specific classes  of neurons in vertebrates (1,2). Careful analysis of
their expression  pattern has revealed a striking coherence which can be
summarized by  three overlapping neuroanatomical correlates: i) all
noradrenergic  neurons, ii) most central and peripheral neurons involved
in the reflex  circuits of the visceral nervous system, iii) cranial
motoneurons.  Published work and ongoing studies aim at reconstructing
the  transcriptional cascades in which Phox2a and Phox2b act and at
defining which part of specific neuronal phenotypes they control (3,4).
The sequencing of the  C. elegans genome has unveiled a probable
orthologue of Phox2a and b,  D1007.1, which we call for the moment
cePhox2. It is 88% identical to  murine Phox2a in the homeodomain, a
level of homology often associated  with functional conservation among
homeobox genes between vertebrates  and invertebrates. We have cloned
the cDNA by RT-PCR, thereby verifying  the GeneFinder prediction. We
have created transgenic lines harboring  GFP under the control of the 1
kb upstream of CePhox2. The transgene is  first expressed in early
embryos. Expression continues at larval and  adult stages in a few head
and tail neurons, and, presumably  ectopically, in the rostral and
caudal part of the intestine. An  antibody raised against the C-terminus
of CePhox2 has confirmed its  neuronal expression. Our current aim is to
identify each Phox2  expressing neuron. We then plan to perform
loss-of-fuction and  gain-of-function studies. Our long-term hope, with
the parallel mouse  and worm studies, is to define what has changed and
what has not  throughout evolution in the "neuro-ontogenetic module"
involving Phox2.    

Thanks to: Alan Coulson, Andy Fire and Theresa Stiernagle.    

(1) Tiveron et al. (1996) J. Neurosci., 16, 7649-7660.
(2) Pattyn et al. (1997) Development, 124, 4065-4075.
(3) Morin et al. (1997) Neuron, 18, 411-423.
(4) Hirsch et al. (1998) Development, 125, 599-608.