Brito José M, Teillet Marie-Aimée, Le Douarin Nicole M
Laboratoire de Développement, Evolution et Plasticité du Système Nerveux, Unité Propre de Recherche 2197, Centre National de la Recherche Scientifique, Institut de Neurobiologie Alfred Fessard, F-91198 Gif-sur-Yvette, France.
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11607-12. doi: 10.1073/pnas.0604751103. Epub 2006 Jul 25.
We have investigated the role of Sonic hedgehog (Shh) in the development of facial structures by depriving chicken embryos of the most anterior sources of this morphogen, including the prechordal plate and the anterior ventral endoderm of the foregut, before the onset of neural crest cell (NCC) migration to the first branchial arch (BA1). The entire forehead, including the foregut endoderm, was removed at 5- to 10-somite stage (ss), which led to the absence of the lower jaw when the operation was performed before 7-ss. If the embryos were deprived of their forehead at 8- to 10-ss, they were later on endowed with a lower beak. In embryos that were operated on early, the NCCs migrated normally to BA1 but were subjected to massive apoptosis a few hours later. Cell death did not occur when forehead excision was performed at a later stage. In this case, onward expression of Shh in the ventral foregut endoderm extended caudally over the excision limit, and we hypothesized that absence of Shh production by the endoderm in embryos that were operated on early could be responsible for the NCC apoptosis and the failure of BA1 development. We thus provided exogenous Shh to the embryos that were operated on before 7-ss. In this case, the development of the lower jaw was rescued. Therefore, Shh derived from the ventral foregut endoderm ensures the survival of NCCs at a critical stage of BA1 development.
我们通过在神经嵴细胞(NCC)迁移至第一鳃弓(BA1)之前,去除鸡胚中这种形态发生素的最前端来源,包括前索板和前肠的腹侧内胚层,来研究音猬因子(Shh)在面部结构发育中的作用。在5至10体节期(ss)去除整个前额,包括前肠内胚层,若手术在7体节之前进行,会导致下颌缺失。若在8至10体节期剥夺胚胎的前额,它们随后会发育出下喙。在早期接受手术的胚胎中,NCC正常迁移至BA1,但数小时后会发生大量细胞凋亡。若在后期进行前额切除,则不会发生细胞死亡。在这种情况下,前肠腹侧内胚层中Shh的后续表达会向尾侧延伸超过切除界限,我们推测早期接受手术的胚胎中内胚层缺乏Shh产生可能是NCC凋亡和BA1发育失败的原因。因此,我们为在7体节之前接受手术的胚胎提供外源性Shh。在这种情况下,下颌的发育得以挽救。所以,源自前肠腹侧内胚层的Shh可确保NCC在BA1发育的关键阶段存活。