Crispino J D, Lodish M B, Thurberg B L, Litovsky S H, Collins T, Molkentin J D, Orkin S H
Division of Hematology and Oncology, Children's Hospital, Boston, Massachusetts 02115, USA.
Genes Dev. 2001 Apr 1;15(7):839-44. doi: 10.1101/gad.875201.
GATA-family transcription factors are critical to the development of diverse tissues. In particular, GATA-4 has been implicated in formation of the vertebrate heart. As the mouse Gata-4 knock-out is early embryonic lethal because of a defect in ventral morphogenesis, the in vivo function of this factor in heart development remains unresolved. To search for a requirement for Gata4 in heart development, we created mice harboring a single amino acid replacement in GATA-4 that impairs its physical interaction with its presumptive cardiac cofactor FOG-2. Gata4(ki/ki) mice die just after embryonic day (E) 12.5 exhibiting features in common with Fog2(-/-) embryos as well as additional semilunar cardiac valve defects and a double-outlet right ventricle. These findings establish an intrinsic requirement for GATA-4 in heart development. We also infer that GATA-4 function is dependent on interaction with FOG-2 and, very likely, an additional FOG protein for distinct aspects of heart formation.
GATA家族转录因子对多种组织的发育至关重要。特别是，GATA-4与脊椎动物心脏的形成有关。由于小鼠Gata-4基因敲除因腹侧形态发生缺陷而导致早期胚胎致死，该因子在心脏发育中的体内功能仍未明确。为了探究Gata4在心脏发育中的需求，我们构建了在GATA-4中存在单个氨基酸替换的小鼠，该替换损害了其与假定的心脏辅因子FOG-2的物理相互作用。Gata4(ki/ki)小鼠在胚胎第12.5天之后死亡，表现出与Fog2(-/-)胚胎共同的特征以及额外的半月形心脏瓣膜缺陷和右心室双出口。这些发现确立了心脏发育中对GATA-4的内在需求。我们还推断，GATA-4的功能依赖于与FOG-2的相互作用，并且很可能还依赖于另一种FOG蛋白来参与心脏形成的不同方面。
