Nemec Stephen, Sung Aurélie Huang, Drouin Jacques
Laboratoire de Génétique Moléculaire, Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7; Department of Experimental Medicine, McGill University, Montreal, QC, Canada H4A 3J1.
Laboratoire de Génétique Moléculaire, Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7.
Dev Biol. 2018 Jul 15;439(2):65-68. doi: 10.1016/j.ydbio.2018.04.024. Epub 2018 Apr 27.
Forelimbs (FLs) and hindlimbs (HLs) develop under the instructive and integrated guidance of signaling centers and transcription factor (TF) action. The development of structures specific to each limb type depends on the limb-specific modulation of these integrated components. Pitx1 is a transcription factor gene expressed in HL, absent in FL, and required for HL-specific patterning and development, in particular for formation of anterior HL skeletal elements. Pitx1 achieves this function by direct TF action on the core limb program, which is largely shared between FL and HL. Shh signaling plays a crucial role in anterior-posterior (AP) patterning in both FL and HL. The present work assessed the relationship between Shh signaling and Pitx1 action for AP patterning. We found that reducing the gene dosage of Shh in the context of the Pitx1-/- HL decreases the severity of the Pitx1-/- phenotype, in particular, the loss of anterior limb structures and the shortening of femur length. However, this did not rescue HL-specific patterning features. Thus, Pitx1 action integrates Shh signaling but not for limb-type-specific patterning.
前肢（FLs）和后肢（HLs）在信号中心和转录因子（TF）作用的指导性和综合性引导下发育。每种肢体类型特有的结构发育取决于这些综合成分的肢体特异性调节。Pitx1是一种在后肢中表达、在前肢中不存在的转录因子基因，是后肢特异性模式形成和发育所必需的，特别是对于前肢后骨骼元素的形成。Pitx1通过对核心肢体程序的直接TF作用来实现这一功能，该程序在前肢和后肢中基本相同。Shh信号在前肢和后肢的前后（AP）模式形成中都起着关键作用。本研究评估了Shh信号与Pitx1在AP模式形成中的作用之间的关系。我们发现，在Pitx1-/-后肢的背景下降低Shh的基因剂量会降低Pitx1-/-表型的严重程度，特别是前肢结构的缺失和股骨长度的缩短。然而，这并没有挽救后肢特异性模式形成特征。因此，Pitx1的作用整合了Shh信号，但不是用于肢体类型特异性模式形成。
