The metalloendopeptidase gene Pitrm1 is regulated by hedgehog signaling in the developing mouse limb and is expressed in muscle progenitors

Dev Dyn. 2009 Dec;238(12):3175-84. doi: 10.1002/dvdy.22126.


Pitrm1 is a zinc metalloendopeptidase that has been implicated in Alzheimer's disease and mitochondrial peptide degradation, but to date no major role in embryonic development has been documented. In a screen for genes regulated by hedgehog signaling in the mouse limb, we showed that expression of Pitrm1 is upregulated in response to loss of the Gli3 transcription factor. Here we confirm spatial changes in Pitrm1 expression in the Gli3 mutant mouse limb and examine Pitrm1 expression in Shh null and Ptch1 conditional deletion mouse mutants. In wild-type mice, Pitrm1 is expressed in a number of developing tissues known to be patterned by Sonic hedgehog, including the limbs, face, cortex, hippocampus, cerebellum, tectum, sub-mandibular gland, lung, genital tubercle, hair follicles, and the enamel knot of the teeth. Additionally, Pitrm1 is expressed in Pax3-expressing myoblast progenitors in the limb, the dermomyotome, and developing muscles of the face and torso.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Mammalian
  • Extremities / embryology*
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Hedgehog Proteins / physiology*
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / metabolism
  • Mice
  • Mice, Transgenic
  • Muscle, Skeletal / embryology*
  • Muscle, Skeletal / metabolism
  • Myoblasts, Skeletal / metabolism
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / metabolism
  • Signal Transduction / genetics
  • Stem Cells / metabolism*
  • Tissue Distribution


  • Hedgehog Proteins
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Shh protein, mouse
  • Pax3 protein, mouse
  • Metalloendopeptidases
  • Pitrm1 protein, mouse