The second site of neural fold bending as described in Section 8.2 and Figure 3(c) is the dorsolateral hinge point (DLHP). Bending of the neuroepithelium at the DLHP is regulated by mutually antagonistic signals external to the neural fold, as reviewed by Greene and Copp [224, 289]. In contrast to midline bending, Shh has been shown to inhibit dorsolateral bending in the mouse  consistent with an absence of NTDs in Shh-null embryos. Signal(s) arising from the surface ectoderm (SE) comprise(s) a second antagonistic signal involved in the regulation and formation of the DLHPs . This has been suggested as further evidence that bending of the neural folds involves signaling from the SE. Bone morphogenetic proteins (BMPs) are candidates to mediate this signaling. Three BMPs (BMP2, BMP4, and BMP7) are expressed in the spinal neural tube. BMP2 and BMP7 are expressed in the surface ectoderm adjacent to the open spinal neural tube, while BMP4 is expressed in the surface ectoderm overlying the closed spinal neural tube .