Shh signaling influences the phenotype of Pitx1-/- hindlimbs

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.

Keywords: Left-right asymmetry; Limb identity; Patterning; Skeletal development; Sonic hedgehog.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Extremities / embryology
  • Forelimb / embryology
  • Forelimb / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Hedgehog Proteins / genetics*
  • Hedgehog Proteins / metabolism
  • Hedgehog Proteins / physiology*
  • Hindlimb / embryology
  • Hindlimb / metabolism
  • Homeodomain Proteins / metabolism
  • Limb Buds / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*
  • Paired Box Transcription Factors / physiology
  • Phenotype
  • Signal Transduction / genetics
  • Transcription Factors / metabolism


  • Hedgehog Proteins
  • Homeodomain Proteins
  • Paired Box Transcription Factors
  • Shh protein, mouse
  • Transcription Factors
  • homeobox protein PITX1