Lam Wee L, Oh Julia D H, Johnson Edward J, Pertinez Sandra Poyatos, Stephens Chloe, Davey Megan G
1 Royal Hospital for Sick Children, Edinburgh, UK.
2 Division of Developmental Biology, University of Edinburgh, Edinburgh, UK. In collaboration with Roslin Institute Chicken Embryology (RICE).
J Hand Surg Eur Vol. 2019 Jan;44(1):43-50. doi: 10.1177/1753193418762959. Epub 2018 Mar 27.
Preaxial polydactyly is a congenital hand anomaly predominantly of sporadic occurrence, which is frequently associated with abnormalities of the Sonic hedgehog signalling pathway. In experimentally induced preaxial polydactyly, radial aplasia is also frequently observed. To determine if there is a correlation between preaxial polydactyly and radial aplasia, we induced ectopic Sonic hedgehog signalling during chicken limb development with application of a smoothened-agonist (SAG) or retinoic acid. Application of SAG caused malformations in 71% limbs including preaxial polydactyly (62%) and forearm abnormalities (43%). Retinoic acid application induced malformations in 56% of limb including preaxial polydactyly (45%) and forearm abnormalities (50%). Radial dysplasia and ulnar dimelia were observed in both experimental conditions. We demonstrate that ectopic Sonic hedgehog signalling may cause both preaxial polydactyly and predictable forearm anomalies and that these conditions could potentially be classified as one embryological group. We propose a unifying model based on known models of ectopic Sonic hedgehog signalling.
轴前多指畸形是一种主要散发出现的先天性手部异常，常与音猬因子信号通路异常相关。在实验诱导的轴前多指畸形中，也经常观察到桡骨发育不全。为了确定轴前多指畸形与桡骨发育不全之间是否存在关联，我们在鸡胚肢体发育过程中通过应用 smoothened 激动剂（SAG）或视黄酸来诱导异位音猬因子信号。应用 SAG 导致 71%的肢体出现畸形，包括轴前多指畸形（62%）和前臂异常（43%）。应用视黄酸诱导 56%的肢体出现畸形，包括轴前多指畸形（45%）和前臂异常（50%）。在两种实验条件下均观察到桡骨发育不良和尺骨重复畸形。我们证明异位音猬因子信号可能导致轴前多指畸形和可预测的前臂异常，并且这些情况可能潜在地归为一个胚胎学组。我们基于已知的异位音猬因子信号模型提出了一个统一模型。
