Kioussi C, O'Connell S, St-Onge L, Treier M, Gleiberman A S, Gruss P, Rosenfeld M G
Howard Hughes Medical Institute, University of California San Diego, School, Department of Medicine, 9500 Gilman Drive, Cellular and Molecular Medicine Room 345, La Jolla, CA 92093-0648, USA.
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14378-82. doi: 10.1073/pnas.96.25.14378.
Pax6, a highly conserved member of the paired homeodomain transcription factor family that plays essential roles in ocular, neural, and pancreatic development and effects asymmetric transient dorsal expression during pituitary development, with its expression extinguished before the ventral --> dorsal appearance of specific cell types. Analysis of pituitary development in the Small eye and Pax6 -/- mouse mutants reveals that the dorsoventral axis of the pituitary gland becomes ventralized, with dorsal extension of the transcriptional determinants of ventral cell types, particularly PFrk. This ventralization is followed by a marked decrease in terminally differentiated dorsal somatotrope and lactotrope cell types and a marked increase in the expression of markers of the ventral thyrotrope cells and SF-1-expressing cells of gonadotrope lineage. We suggest that the transient dorsal expression of Pax6 is essential for establishing a sharp boundary between dorsal and ventral cell types, based on the inhibition of Shh ventral signals.
Pax6是配对同源结构域转录因子家族中高度保守的成员,在眼睛、神经和胰腺发育中起关键作用,并在垂体发育期间引起不对称的短暂背侧表达,其表达在特定细胞类型腹侧→背侧出现之前消失。对小眼和Pax6 -/-小鼠突变体垂体发育的分析表明,垂体的背腹轴腹侧化,腹侧细胞类型(特别是PFrk)的转录决定因子向背侧延伸。这种腹侧化之后,终末分化的背侧生长激素细胞和催乳激素细胞类型显著减少,腹侧促甲状腺激素细胞和促性腺激素谱系中表达SF-1的细胞标志物的表达显著增加。我们认为,基于对Shh腹侧信号的抑制,Pax6的短暂背侧表达对于在背侧和腹侧细胞类型之间建立清晰边界至关重要。