Piotrowski Tatjana, Ahn Dae-gwon, Schilling Thomas F, Nair Sreelaja, Ruvinsky Ilya, Geisler Robert, Rauch Gerd-Jörg, Haffter Pascal, Zon Leonard I, Zhou Yi, Foott Helen, Dawid Igor B, Ho Robert K
National Institutes of Health, NICHD, LMG, Bldg. 6B, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Development. 2003 Oct;130(20):5043-52. doi: 10.1242/dev.00704.
The van gogh (vgo) mutant in zebrafish is characterized by defects in the ear, pharyngeal arches and associated structures such as the thymus. We show that vgo is caused by a mutation in tbx1, a member of the large family of T-box genes. tbx1 has been recently suggested to be a major contributor to the cardiovascular defects in DiGeorge deletion syndrome (DGS) in humans, a syndrome in which several neural crest derivatives are affected in the pharyngeal arches. Using cell transplantation studies, we demonstrate that vgo/tbx1 acts cell autonomously in the pharyngeal mesendoderm and influences the development of neural crest-derived cartilages secondarily. Furthermore, we provide evidence for regulatory interactions between vgo/tbx1 and edn1 and hand2, genes that are implicated in the control of pharyngeal arch development and in the etiology of DGS.
斑马鱼中的梵高（vgo）突变体的特征是耳朵、咽弓及相关结构（如胸腺）存在缺陷。我们发现vgo是由T-box基因大家族成员tbx1中的一个突变引起的。最近有人提出，tbx1是导致人类22q11.2缺失综合征（DGS）中心血管缺陷的主要因素，在该综合征中，咽弓中的几种神经嵴衍生物会受到影响。通过细胞移植研究，我们证明vgo/tbx1在咽中胚层中自主发挥作用，并继而影响神经嵴衍生软骨的发育。此外，我们提供了vgo/tbx1与edn1和hand2之间调控相互作用的证据，这些基因与咽弓发育的控制以及DGS的病因学有关。
