Neural expression of the Huntington's disease gene as a chordate evolutionary novelty.
Huntington's disease is a progressive neuro-degenerative disorder in humans, which is scharacterized by onset of dementia, muscular ataxia, and death. Huntington's disease is caused by the expansion of the polyglutamine (polyQ) tract in the N-terminus of the HD protein (Huntingtin). CAG expansion is a dominant gain of function mutation that affects striated neurons in the brain (Cattaneo, 2003, News Physiol Sci 18:34). The evolutionary origins of the vertebrate Hd gene are not well understood. In order to address the evolutionary history of the Hd gene, we have cloned and characterized the expression of the Hd gene in two invertebrate deuterostomes, an echinoderm and an ascidian, and have examined the expression patterns in a phylogenetic context. Echinoderms are basal deuterostomes and ascidians are basal chordates; both are useful for understanding the origins of and evolutionary trends in genes important in vertebrates such as the Huntigton's disease gene. Expression of Hd RNA is detected at all stages of development in both the echinoderm and ascidian studied. In the echinoderm Heliocidaris erythrogramma, Hd is expressed in coelomic mesodermal tissue derivatives, but not in the central nervous system. In the ascidian Halocynthia roretzi expression is located in both mesoderm and nervous tissue. We suggest that the primitive deuterostome expression pattern is not neural. Thus, neural expression of the Hd gene in deuterostomes may be a novel feature of the chordate lineage, and the original role(s) of HD in deuterostomes may have been non-neural.
Kauffman
Jeffrey S
JS
Department of Biology, Indiana University, Bloomington, Indiana 47405, USA.
Zinovyeva
Anna
A
Yagi
Kasumi
K
Makabe
Kazuhiro W
KW
Raff
Rudolf A
RA
D000595:Amino Acid Sequence; D000818:Animals; D002816:Chordata, Nonvertebrate / Q000235:genetics*; D004447:Echinodermata / Q000235:genetics*; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010802:Phylogeny
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins