Yevtodiyenko Aleksey, Schmidt Jennifer V
Department of Biological Sciences, The University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, USA.
Dev Dyn. 2006 Apr;235(4):1115-23. doi: 10.1002/dvdy.20705.
The protein product of the Delta-like 1 (Dlk1) gene belongs to the Delta-Notch family of signaling molecules, proteins involved in cell fate determination in many tissues during development. The DLK1 protein is believed to function as a growth factor, maintaining the proliferative state of undifferentiated cells, and is usually down-regulated as immature cells differentiate. The expression pattern of the DLK1 protein has been described in certain human tissues; however, Dlk1 expression is not well understood in the mouse, the most tractable mammalian genetic model system. To better understand the role of Dlk1 in embryonic development, the tissue-specific expression pattern of Dlk1 mRNA during mouse embryogenesis was analyzed by in situ hybridization. In embryonic day 12.5 (e12.5) embryos, high levels of Dlk1 were found in the developing pituitary, pancreas, lung, adrenal, and many mesodermally derived tissues. Strikingly, Dlk1 expression also marks the growing branches of organs that develop through the process of branching morphogenesis. At e16.5, Dlk1 expression is down-regulated in most tissues but remains in the pituitary, the adrenal gland, and in skeletal muscle. In the placenta, expression of Dlk1 is detected in endothelial cells lining the fetal blood vessels of the labyrinth. This pattern is distinct from that seen in the human placenta and suggests a role for Dlk1 in regulating maternal-fetal interactions.
Delta样1(Dlk1)基因的蛋白质产物属于Delta-Notch信号分子家族,这类蛋白质在发育过程中参与多种组织细胞命运的决定。DLK1蛋白被认为具有生长因子的功能,维持未分化细胞的增殖状态,并且通常在未成熟细胞分化时下调。DLK1蛋白的表达模式已在某些人类组织中有所描述;然而,在小鼠这个最易处理的哺乳动物遗传模型系统中,Dlk1的表达情况尚未得到充分了解。为了更好地理解Dlk1在胚胎发育中的作用,通过原位杂交分析了小鼠胚胎发育过程中Dlk1 mRNA的组织特异性表达模式。在胚胎第12.5天(e12.5)的胚胎中,在发育中的垂体、胰腺、肺、肾上腺以及许多中胚层来源的组织中发现了高水平的Dlk1。引人注目的是,Dlk1的表达也标记了通过分支形态发生过程发育的器官的生长分支。在e16.5时,Dlk1在大多数组织中的表达下调,但在垂体、肾上腺和骨骼肌中仍然存在。在胎盘中,在迷路胎儿血管内衬的内皮细胞中检测到Dlk1的表达。这种模式与人类胎盘中观察到的不同,提示Dlk1在调节母胎相互作用中发挥作用。