Griffin K J, Stoller J, Gibson M, Chen S, Yelon D, Stainier D Y, Kimelman D
Department of Biochemistry, University of Washington, Seattle, Washington 98195-7350, USA.
Dev Biol. 2000 Feb 15;218(2):235-47. doi: 10.1006/dbio.1999.9571.
T-box transcription factors are critical regulators of early embryonic development. We have characterized a novel zebrafish T-box transcription factor, hrT (H15-related T box) that is a close relative of Drosophila H15 and a recently identified human gene. We show that Drosophila H15 and zebrafish hrT are both expressed early during heart formation, in strong support of previous work postulating that vertebrate and arthropod hearts are homologous structures with conserved regulatory mechanisms. The timing and regulation of zebrafish hrT expression in anterior lateral plate mesoderm suggest a very early role for hrT in the differentiation of the cardiac precursors. hrT is coexpressed with gata4 and nkx2.5 not only in anterior lateral plate mesoderm but also in noncardiac mesoderm adjacent to the tail bud, suggesting that a conserved regulatory pathway links expression of these three genes in cardiac and noncardiac tissues. Finally, we analyzed hrT expression in pandora mutant embryos, since these have defects in many of the tissues that express hrT, including the heart. hrT expression is much reduced in the early heart fields of pandora mutants, whereas it is ectopically expressed subsequently. Using hrT expression as a marker, we describe a midline patterning defect in pandora affecting the anterior hindbrain and associated midline mesendodermal derivatives. We discuss the possibility that the cardiac ventricular defect previously described in pandora and the midline defects described here are related.
T-box转录因子是早期胚胎发育的关键调节因子。我们鉴定了一种新的斑马鱼T-box转录因子hrT(H15相关T盒),它是果蝇H15的近亲,也是最近鉴定出的一个人类基因。我们发现果蝇H15和斑马鱼hrT在心脏形成早期均有表达,有力支持了先前的研究,即脊椎动物和节肢动物的心脏是具有保守调节机制的同源结构。斑马鱼hrT在前侧板中胚层的表达时间和调控表明hrT在心脏前体细胞的分化中起非常早期的作用。hrT不仅与gata4和nkx2.5在前侧板中胚层共表达,而且在尾芽附近的非心脏中胚层也共表达,这表明一条保守的调控途径将这三个基因在心脏和非心脏组织中的表达联系起来。最后,我们分析了hrT在pandora突变胚胎中的表达,因为这些胚胎在许多表达hrT的组织中存在缺陷,包括心脏。hrT在pandora突变体的早期心脏区域表达大大降低,而随后会异位表达。以hrT表达为标记,我们描述了pandora中影响前脑后部和相关中胚层中线衍生物的中线模式缺陷。我们讨论了先前在pandora中描述的心室缺陷与这里描述的中线缺陷相关的可能性。