INVESTIGADORES
DOMENE Sabina
congresos y reuniones científicas
Título:
Dissecting the function of the homeodomain transcription factor Rax during hypothalamic development
Autor/es:
DANIELA ORQUERA; SOFIA NASIF; SABINA DOMENE; MALCOLM LOW; MARCELO RUBINSTEIN; FLAVIO JUNQUEIRA
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.