Carreno Gabriela, Apps John R, Lodge Emily J, Panousopoulos Leonidas, Haston Scott, Gonzalez-Meljem Jose Mario, Hahn Heidi, Andoniadou Cynthia L, Martinez-Barbera Juan Pedro
Developmental Biology and Cancer Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Centre for Craniofacial and Regenerative Biology, King's College London, London SE1 9RT, UK.
Development. 2017 Sep 15;144(18):3289-3302. doi: 10.1242/dev.153387. Epub 2017 Aug 14.
Sonic hedgehog (SHH) is an essential morphogenetic signal that dictates cell fate decisions in several developing organs in mammals. data suggest that SHH is required to specify LHX3/LHX4 Rathke's pouch (RP) progenitor identity. However, studies have failed to reveal such a function, supporting instead a crucial role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3/LHX4 RP identity in mouse embryos. First, we show that conditional deletion of in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of RP development, with lack of expression in RP epithelium at 9.0 days post coitum (dpc) and total loss of pituitary tissue by 12.5 dpc. Conversely, overactivation of the SHH pathway by conditional deletion of in RP progenitors leads to severe hyperplasia and enlargement of the Sox2 stem cell compartment by the end of gestation.
音猬因子（SHH）是一种重要的形态发生信号，它决定了哺乳动物多个发育器官中的细胞命运决定。数据表明，SHH是确定LHX3/LHX4拉特克囊（RP）祖细胞身份所必需的。然而，研究未能揭示出这样一种功能，反而支持SHH在促进这些RP祖细胞增殖以及垂体细胞类型分化中起关键作用。在这里，我们采用遗传学方法证明，SHH信号通路的激活对于在小鼠胚胎中诱导LHX3/LHX4 RP身份是必要的。首先，我们表明，下丘脑前部中 的条件性缺失导致一种完全显性的表型，其特征是RP发育完全停滞，在交配后9.0天（dpc）时RP上皮中缺乏 表达，到12.5 dpc时垂体组织完全丧失。相反，通过在RP祖细胞中条件性缺失 来过度激活SHH信号通路，会导致妊娠末期Sox2干细胞区室严重增生和扩大。
