Recent studies suggest that Noggin may also play a role in regulating DLHP formation [292, 293]. Noggin is an inhibitor of BMP signaling and is expressed at the tips of the apposing neural folds [293, 294]. Homozygous mouse embryos null for Noggin exhibit both exencephaly and spina bifida (100%) [292, 295]. However, spina bifida does not arise in homozygous Noggin mutants until embryonic day 11-12 when the neural tube ruptures. The spinal neural tube of homozygous null Noggin embryos during neurulation takes on the appearance of a wavy neural tube before the neural tube reopens , possibly suggesting an unstable initial closure mechanism. Shh works in an antagonistic manner towards Noggin, as does Noggin towards BMP signaling . This suggests that Noggin may facilitate bending of the spinal neural tube  by overcoming the inhibitory influence of BMPs.