Hidalgo-Sánchez Matías, Alvarado-Mallart Rosa-Magda
INSERM U-106, Hôpital de la Salpêtrière, Pavillon Enfants et Adolescents, Paris, France.
Dev Dyn. 2002 Jan;223(1):141-7. doi: 10.1002/dvdy.1224.
Transplantation of prosomeres 1-2 into the cerebellar plate were used, by using chick/quail chimeras, to analyse the temporal sequence of the genetic cascade leading the graft to develop a midbrain/hindbrain phenotype. Our results show that (1) at Hamburger and Hamilton (HH) stage 13, Pax2 and En2 are already induced within the graft, before all other genes of the cascade, whereas misexpression of Fgf8 is also observed within the contiguous host cerebellar plate; (2) within the graft, Otx2 repression and Gbx2 induction (see Hidalgo-Sánchez et al. [1999] Development 126:3191-3203) are secondary events that affect, from stages HH14-15, the areas in contact with the host Gbx2/Fgf8-expressing cerebellar plate; (3) at these stages, the repressed Otx2 territory extends beyond the areas induced to express Gbx2, with the two territories not abutting before HH17-18; (4) Fgf8 expression becomes progressively induced within the Otx2-repressed/Gbx2-induced territory, starting at HH15-16. Our results support the hypothesis that the host-Gbx2/graft-Otx2 interface could trigger the genetic cascade induced within the graft and that the Gbx2-induced domain could play a key role during the establishment of the induced intragraft midbrain/hindbrain boundary.
通过使用鸡/鹌鹑嵌合体,将前脑原节1-2移植到小脑板中,以分析导致移植物发育出中脑/后脑表型的基因级联反应的时间顺序。我们的结果表明:(1)在汉堡和汉密尔顿(HH)第13阶段,移植物内的Pax2和En2在级联反应的所有其他基因之前就已被诱导,而在相邻的宿主小脑板内也观察到Fgf8的错误表达;(2)在移植物内,Otx2的抑制和Gbx2的诱导(见伊达尔戈-桑切斯等人[1999年]《发育》126:3191-3203)是次级事件,从HH14-15阶段开始,影响与表达宿主Gbx2/Fgf8的小脑板接触的区域;(3)在这些阶段,被抑制的Otx2区域延伸到诱导表达Gbx2的区域之外,这两个区域在HH17-18之前并不相邻;(4)从HH15-16阶段开始,Fgf8表达在Otx2抑制/Gbx2诱导的区域内逐渐被诱导。我们的结果支持这样的假设,即宿主-Gbx2/移植物-Otx2界面可能触发移植物内诱导的基因级联反应,并且Gbx2诱导的区域可能在移植物内诱导的中脑/后脑边界的建立过程中起关键作用。