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[P146]: Redundant functions of Fgfr1, Fgfr2 and Fgfr3 in the development of the mid‐ and hindbrain
Author(s) -
SaarimäkiVire J.,
Peltopuro P.,
Blak A.,
Lahti L.,
Ornitz D.,
Wurst W.,
Partanen J.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.207
Subject(s) - research center , library science , center (category theory) , political science , gerontology , medicine , law , computer science , chemistry , crystallography
Hesx1 that are involved in specifying the anterior neurectoderm are unknown. We have previously shown that mouse embryonic stem cells differentiated as aggregates in HepG2 cell conditioned medium, synchronously and homogeneously differentiate to a midbrainlike population of neurectoderm cells. Analysis of ES cellderived neurectoderm suggest that it has not been exposed to patterning signals, such as the ventralising signal Sonic Hedgehog, making it a powerful tool for identifying and characterising molecules involved in neural tube patterning. We have exploited these characteristics to understand the signalling molecules that emanate from the AVE and anteriorise the neurectoderm. Hesx1 was over-expressed in HepG2 cells (HepG2:Hesx1) and the conditioned medium tested for the ability to anteriorise ES cell-derived neurectoderm. After 2 days, in presence of HepG2:Hesx1 CM anterior markers were up-regulated in the neurectoderm, suggesting that the CM contained signals that anteriorise neurectoderm. Microarray analysis was performed on HepG2 and HepG2:Hesx1 cells to identify differentially expressed genes. Of the four secreted molecules identified one growth factor was chosen for further characterisation. Addition of recombinant growth factor to ES cell-derived neurectoderm resulted in up-regulation of anterior markders, indicating that this growth factor is involved in anteriorising neural progenitors. In addition, expression analysis showed this growth factor is present in the AVE of 6.5 and 7.5 dpc mouse embryos suggesting a mechanism by which Hesx1 expression in the AVE regulates the positional specification of the anterior neurectoderm and forebrain.