Expression of the sonic hedgehog gene in human embryos with neural tube defects

Background: To estimate the rate of malformations observed during early hum an development, a series of 38,913 first-trimester abortions were studied. Neural tube defects (NTD) were found in 57 cases. Methods: A histological study of serial sections performed in 25 embryos re vealed a spectrum of axial structure abnormalities. Expression of the SHH g ene was studied by in situ hybridization in one case of CRS and in two case s of SE. Results: A cervical notochord duplication was always found in craniorachisc hisis (CRS, n = 8), but not in spina bifida (SB, n = 10) or diplomyelia (sp lit cord malformation, n = 3). in the embryo with CRS, expression of SHH wa s found in both domains, corresponding to the duplicated part of the notoch ord, whereas a single signal was observed in the nonduplicated part. This e xpression was associated at the cervical level of the open neural tube with a broad SHH expression domain and with two or even three domains in its lu mbar region, suggesting multiple functional floor plates. Similarly, in two embryos with SE, two domains of SHH expression were found in the ventral n eural tube. Conclusions: Our findings suggest that notochord splitting in the cervical region might be involved in the pathogenesis of CRS. Interestingly, similar notochord abnormality and altered expression of the shh gene are observed in Lp mice with NTI). This suggests that the Lp gene could be a candidate g ene for human CRS. Further studies are needed to establish the primary even t responsible for the notochord splitting and for the abnormal expression o f the SHH gene in the floor plate in embryos with CRS and SE. (C) 2000 Wile y-Liss, Inc.