Functional equivalence of the transcription factors Pax2 and Pax5 in mousedevelopment

Citation
M. Bouchard et al., Functional equivalence of the transcription factors Pax2 and Pax5 in mousedevelopment, DEVELOPMENT, 127(17), 2000, pp. 3703-3713
Citations number
58
Categorie Soggetti
Cell & Developmental Biology
Journal title
DEVELOPMENT
ISSN journal
09501991 → ACNP
Volume
127
Issue
17
Year of publication
2000
Pages
3703 - 3713
Database
ISI
SICI code
0950-1991(200009)127:17<3703:FEOTTF>2.0.ZU;2-M
Abstract
Pax2 and Pax5 arose by gene duplication at the onset of vertebrate evolutio n and have since diverged in their developmental expression patterns. They are expressed in different organs of the mouse embryo except for their coex pression at the midbrain-hindbrain boundary (MHB), which functions as an or ganizing center to control midbrain and cerebellum development. During MHB development, Pax2 expression is initiated prior to Pax5 transcription, and Pax2(-/-) embryos fail to generate the posterior midbrain and cerebellum, w hereas Pax5(-/-) mice exhibit only minor patterning defects in the same bra in regions. To investigate whether these contrasting phenotypes are caused by differences in the temporal expression or biochemical activity of these two transcription factors, we have generated a knock-in (ki) mouse, which e xpresses a Pax5 minigene under the control of the Pax2 locus. Midbrain and cerebellum development was entirely rescued in Pax2(5ki/5ki) embryos. Pax5 could furthermore completely substitute for the Pax2 function during morpho genesis of the inner ear and genital tracts, despite the fact that the Pax5 transcript of the Par2(5ki) allele was expressed only at a fivefold lower level than the wildtype Pax2 mRNA, As a consequence, the Pax2(5ki) allele w as able to rescue most but not all Pax2 mutant defects in the developing ey e and kidney, both of which are known to be highly sensitive to Pax2 protei n dosage, Together these data demonstrate that the transcription factors Pa x2 and Pax5 have maintained equivalent biochemical functions since their di vergence early in vertebrate evolution.