Expressions of BMP Antagonists in Shh -/- ; Gli3 -/- Mutant

Oh, Sae Ock; Moon, Yong Suk; Bae, Soo Kyung; Yoon, Sik; Baek, Sun Yong; Kim, Bong Seon; Kim, Jae Bong

Abstract

Sonic hedgehog (Shh) has been known as an essential morphogen for the generation of motor neuron in developing spinal cord. However, motor neuron can be generated in Shh -/- ; Gli3 -/- or Gli2 -/- ; Gli3 -/- mutants although these mutants don't have Shh signaling. To find out the compensatory mechanism for the generation of motor neuron in Shh -/- ; Gli3 -/- mutant, we studied bone morphogenetic protein (BMP) antagonists including follistatin, flik and noggin, and retinoic acid signaling in this mutant. To study expressions of BMP antagonists, we performed in situ hybridization. To examine an activity of retinoic acid, we measured beta -galactosidase activity in retinoic acid response element (RARE) transgenic mouse. The expression of follistatin was reduced at both levels of forelimb and hindlimb in Shh -/- mutant compared to wild type embryo. It was restored at the level of forelimb but reduced at the level of hindlimb in Shh -/- ; Gli3 -/- mutant compared to wild type. The expression of flik was similar with wild type embryo at both levels of forelimb and hindlimb in Shh -/- mutant. The expression of flik was similar with wild type embryo at the level of forelimb however reduced in hindlimb level in Shh -/- ; Gli3 -/- mutant. The expression of noggin, a BMP antagonist, was increased in Shh -/- mutant. Activity of retinoic acid signaling was not affected in Shh -/- or Shh -/- ; Gli3 -/- mutants. From these results, we conclude that retinoic acid but not follistatin and flik, may be involved in the generation of motor neuron in Shh -/- ; Gli3 -/- mutant.