Shh signaling influences the phenotype of Pitx1-/- hindlimbs

Developmental biology

Aurélie Huang Sung^1¹  Stephen Nemec^1,2² 

[1] Department of Experimental Medicine, McGill University, Montreal, QC, Canada H4A 3J1^2;Laboratoire de Génétique Moléculaire, Institut de recherches cliniques de Montréal, Montréal, QC, Canada H2W 1R7^1

关键词: Limb identity;    Patterning;    Left-right asymmetry;    Skeletal development;    Sonic hedgehog;   

DOI  :  10.1016/j.ydbio.2018.04.024

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

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.

【 授权许可】

CC BY