Krawchuk Dayana, Kania Artur
Laboratory of Neural Circuit Development, Institut de recherches cliniques de Montréal (IRCM), QC, Canada.
Dev Dyn. 2008 Apr;237(4):1183-92. doi: 10.1002/dvdy.21514.
In the developing limb, dorsal-ventral patterning is controlled by the transcription factor LMX1B, expressed in the dorsal mesenchyme. Loss of Lmx1b function in mice or humans results in the loss of dorsal limb structures and Nail-Patella syndrome, but the effectors through which LMX1B controls limb patterning are virtually unknown. Using microarrays to analyze the differential expression of mRNAs in wild-type vs. Lmx1b(-/-) limb buds, we have identified hundreds of genes as putative LMX1B targets. Analysis of a subset of these candidates by in situ mRNA localization has identified eight genes previously unknown to require Lmx1b for their dorsal-ventral restriction of expression in the limb. Furthermore, our results suggest that LMX1B controls different targets along the proximal-distal axis of the limb, and suggest the existence of a dorsal proximal limb region that is rich in mRNAs requiring Lmx1b for their expression.
在发育中的肢体中,背腹模式由在背侧间充质中表达的转录因子LMX1B控制。小鼠或人类中Lmx1b功能的丧失会导致背侧肢体结构缺失和指甲-髌骨综合征,但LMX1B控制肢体模式的效应器几乎未知。我们使用微阵列分析野生型与Lmx1b(-/-)肢体芽中mRNA的差异表达,已鉴定出数百个基因为假定的LMX1B靶标。通过原位mRNA定位对这些候选基因的一个子集进行分析,已鉴定出八个以前未知的基因,它们在肢体中的背腹表达限制需要Lmx1b。此外,我们的结果表明,LMX1B沿着肢体的近远轴控制不同的靶标,并表明存在一个富含需要Lmx1b表达的mRNA的背侧近端肢体区域。