TY - JOUR
T1 - Murine Otx1 and Drosophila otd genes share conserved genetic functions required in invertebrate and vertebrate brain development
AU - Acampora, Dario
AU - Avantaggiato, Virginia
AU - Tuorto, Francesca
AU - Barone, Paolo
AU - Reichert, Heinrich
AU - Finkelstein, Robert
AU - Simeone, Antonio
PY - 1998
Y1 - 1998
N2 - Despite the obvious differences in anatomy between invertebrate and vertebrate brains, several genes involved in the development of both brain types belong to the same family and share similarities in expression patterns. Drosophila orthodenticle (otd) and murine Otx genes exemplify this, both in terms of expression patterns and mutant phenotypes. In contrast, sequence comparison of OTD and OTX gene products indicates that homology is restricted to the homeodomain suggesting that protein divergence outside the homeodomain might account for functional differences acquired during brain evolution. In order to gain insight into this possibility, we replaced the murine Otx1 gene with a Drosophila otd cDNA. Strikingly, epilepsy and corticogenesis defects due to the absence of Otx1 were fully rescued in homozygous otd mice. A partial rescue was also observed for the impairments of mesencephalon, eye and lachrymal gland. In contrast, defects of the inner ear were not improved suggesting a vertebrate Otx1-specific function involved in morphogenesis of this structure. Furthermore, otd, like Otx1, was able to cooperate genetically with Otx2 in brain patterning, although with reduced efficiency. These data favour an extended functional conservation between Drosophila otd and murine Otx1 genes and support the idea that conserved genetic functions required in mammalian brain development evolved in a primitive ancestor of both flies and mice.
AB - Despite the obvious differences in anatomy between invertebrate and vertebrate brains, several genes involved in the development of both brain types belong to the same family and share similarities in expression patterns. Drosophila orthodenticle (otd) and murine Otx genes exemplify this, both in terms of expression patterns and mutant phenotypes. In contrast, sequence comparison of OTD and OTX gene products indicates that homology is restricted to the homeodomain suggesting that protein divergence outside the homeodomain might account for functional differences acquired during brain evolution. In order to gain insight into this possibility, we replaced the murine Otx1 gene with a Drosophila otd cDNA. Strikingly, epilepsy and corticogenesis defects due to the absence of Otx1 were fully rescued in homozygous otd mice. A partial rescue was also observed for the impairments of mesencephalon, eye and lachrymal gland. In contrast, defects of the inner ear were not improved suggesting a vertebrate Otx1-specific function involved in morphogenesis of this structure. Furthermore, otd, like Otx1, was able to cooperate genetically with Otx2 in brain patterning, although with reduced efficiency. These data favour an extended functional conservation between Drosophila otd and murine Otx1 genes and support the idea that conserved genetic functions required in mammalian brain development evolved in a primitive ancestor of both flies and mice.
KW - Brain
KW - Conserved function
KW - Drosophila
KW - Evolution
KW - Orthodenticle (otd)
KW - Otx1
UR - http://www.scopus.com/inward/record.url?scp=0031830858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031830858&partnerID=8YFLogxK
M3 - Article
C2 - 9521907
AN - SCOPUS:0031830858
VL - 125
SP - 1691
EP - 1702
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 9
ER -