INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Dissecting the function of the homeodomain transcription factor Rax during hypothalamic development
Autor/es:
ORQUERA, DP; NASIF S; DOMENE S; LOW MJ; RUBINSTEIN M*; DE SOUZA FS*
Lugar:
Montevideo
Reunión:
Congreso; VI International Meeting of the Latin American Society for Developmental Biology; 2012
Institución organizadora:
Latin American Society for Developmental Biology
Resumen:
During embryogenesis, brain development is controlled by a complex interplay between signalling molecules and transcription factors that pattern the neural tube and induce its miriads of cell types. The homeobox gene Rx is expressed in the retina and ventral forebrain, and is implicated in the development of these structures, but the severe phenotype of homozygous Rx-null makes it diffult to study. To better understand Rx function, we performed temporal inactivation of the gene during mouse embryogenesis with a "floxed" Rx allele and a Cre recombinase that can be induced by tamoxifen injections at specific time points. Early Rx inactivation at gestational day 7.5 (E7.5) caused lack of eyes and hypothalamic disorganisation, as well as severe forebrain deformities, probably related to its early expression in the opened anterior neural ridge. In contrast, later Rx deletion (E8.0) caused a milder phenotype, without extensive forebrain deformity. Eyes were absent and, at the hypothalamic level, the infundibulum (future neural lobe of the pituitary) did not evaginate. Immunohistochemistry showed that in these embryos the infundibulum region was anteriorised, as evidenced by misexpression of POMC, a marker normally restricted to the region anterior to the infundibulum. Rx inactivation at a later stage (E9.5) did not cause extensive alterations in hypothalamic patterning. We are currently analysing the expression of different marker genes to better characterise the role of Rx in hypothalamic development. In addition to these studies in mice, we also observed that morpholino-mediated knockdown of zebrafish homologue Rx3 interferes with eye and hypothalamic development.