Body segment identity specification by the transcription regulator, Moz

每28个新生儿中就有一个有先天缺陷。腭裂和主动脉弓缺损是最常见的，总是需要手术，往往造成死亡。我们建议研究一种蛋白质Moz，它对腭和主动脉弓的发育至关重要。Moz（单核细胞白血病锌指蛋白）首次在人类染色体异常中发现，导致特别严重的儿童和成人白血病。我们之前已经证明Moz对造血干细胞的形成至关重要。Moz可以调节基因的活性，但它在体内调节哪些基因尚不清楚。在没有Moz的情况下，小鼠出生时有腭裂，缺乏胸腺，免疫细胞在那里接受指导，并且无法形成肺部血液循环，因此它们在出生后无法为血液提供氧气。Moz缺乏也会导致脊椎动物脊柱的缺陷，使得个体椎骨获得其相邻椎骨的外观。这些症状是典型的一般缺陷的位置信息的个别身体部分相对于他们的位置沿着身体轴。我们将调查的分子机制，需要Moz在图案的身体轴。该项目将描述一种遗传机制，这对腭、主动脉和脊椎动物柱的正常发育至关重要。

One in 28 newborns have birth defects. Cleft palate and aortic arch defects are among the most common, always requiring surgery and often causing lethality. We propose to study a protein, Moz, which is essential for palate and aortic arch development. Moz (Monocytic leukaemia zinc finger protein) was first identified in human chromosomal abnormalities causing particularly aggressive forms of childhood and adult leukaemia. We have shown previously that Moz is essential for the formation of blood stem cells. Moz can regulate the activity of genes, but which genes it regulates in vivo is unknown. In the absence of Moz, mice are born with a cleft palate, lack the thymus, where immune cells are instructed, and fail to form the lung blood circulation, so that they are unable to supply their blood with oxygen after birth. Moz deficiency also causes defects of the vertebrate column, such that individual vertebrae acquire the appearance of their neighbours. These symptoms are typical for a general defect in positional information of individual body segments with respect to their location along the body axis. We will investigate the molecular mechanisms that require Moz in patterning of the body axis. This project will characterize a genetic mechanism that is crucial for normal development of the palate, the aorta and the vertebrate column.