Cooperation of Pax2 and Pax5 in midbrain and cerebellum development

Abstract

Midbrain and cerebellum development depends on an organizing center that is located at the midbrainhindbrain junction of the vertebrate embryo. Expression of the two closely related transcription factors Pax2 and Pax5 overlaps spatially and temporally in this region of the developing central nervous system. To study a possible interaction of these transcription factors in midbrain and cerebellum patterning, we have generated Pax5, Krd double mutant mice. The transgene-induced Krd mutation corresponds to an Ϸ7-centimorgan chromosome 19 deletion that eliminates the entire Pax2 locus. The heterozygous Krd mutation deleting one Pax2 allele had no effect on midbrain and cerebellum development. Moreover, only minor developmental defects were previously observed at the midline of the inferior colliculus and anterior cerebellum in mice that were homozygous for a targeted Pax5 mutation. Similar morphological alterations were observed in 80% of all compound heterozygous Pax5 (؉͞؊) Krd (؉͞؊) mice. However, in the remaining 20% of compound heterozygotes, the inferior colliculi were missing, and the vermis of the cerebellum was severely disrupted due to the failure of the cerebellar primordia to fuse at the midline. Inactivation of the second Pax5 allele in Pax5 (؊͞؊) Krd (؉͞؊) mice resulted in complete loss of the posterior midbrain and cerebellum, as the tissue originating from the midbrain-hindbrain boundary region was deleted in the embryo as early as day 9.5. On the basis of these data, we propose that the cooperation of Pax2 and Pax5 is essential for normal functioning of the organizing center at the midbrainhindbrain junction.

The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant neoplasms

“…9 In addition to its expression in B cells, PAX5 protein and/or mRNA has been reported to be expressed in normal and neoplastic cell types in the central nervous system, testis and bladder. 3,[10][11][12][13][14][15] B-cell malignancies may express PAX5 in the absence of expression of other pan-B-cell markers, suggesting that the inclusion of PAX5 in a panel of antibodies to assess undifferentiated malignant neoplasms may have diagnostic benefit. To address this possibility, we studied examples previously diagnosed as undifferentiated malignant neoplasms for PAX5 expression by immunohistologic methods.…”

Expression of Pax2 protein during the formation of the central nervous system in human embryos

“…Several experimental animal studies have suggested that initiation and functioning of this organising centre crucially depends on Pax2 [1,16,22,23], and that the regulatory role of Pax2 is an evolutionarily conserved feature for all vertebrates [14]. Furthermore, it has been shown that a mutation of the Pax2 gene in the isthmus leads to the loss of the midbrain and the cerebellum [3,15,22].…”

Role of Pax-5 Transcription Factor in Immunological Processes

“…В экспериментах с костным мозгом PAX-5 -/-мышей дифференцировка В-клеток останав-ливалась на стадии ранних про-В-клеток [53]. В зависимости от окружения (ростовых факто-ров, стромальных клеток костного мозга) PAX-5 -/-клетки in vitro могут сохранять возможность дифференцировки в разные клетки миелоидно-го и лимфоидного ростков, а при восстановле-нии экспрессии PAX-5 -вновь ограничиваются в возможности развития только в направлении В-лимфоцитов [37].…”