Apical ectodermal ridge regulates three principal axes of the developing limb / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Understanding limb development not only gives insights into the outgrowth and differentiation of the limb, but also has clinical relevance. Limb development begins with two paired limb buds (forelimb and hindlimb buds), which are initially undifferentiated mesenchymal cells tipped with a thickening of the ectoderm, termed the apical ectodermal ridge (AER). As a transitional embryonic structure, the AER undergoes four stages and contributes to multiple axes of limb development through the coordination of signalling centres, feedback loops, and other cell activities by secretory signalling and the activation of gene expression. Within the scope of proximodistal patterning, it is understood that while fibroblast growth factors (FGFs) function sequentially over time as primary components of the AER signalling process, there is still no consensus on models that would explain proximodistal patterning itself. In anteroposterior patterning, the AER has a dual-direction regulation by which it promotes the sonic hedgehog (Shh) gene expression in the zone of polarizing activity (ZPA) for proliferation, and inhibits Shh expression in the anterior mesenchyme. In dorsoventral patterning, the AER activates Engrailed-1 (En1) expression, and thus represses Wnt family member 7a (Wnt7a) expression in the ventral ectoderm by the expression of Fgfs, Sp6/8, and bone morphogenetic protein (Bmp) genes. The AER also plays a vital role in shaping the individual digits, since levels of Fgf4/8 and Bmps expressed in the AER affect digit patterning by controlling apoptosis. In summary, the knowledge of crosstalk within AER among the three main axes is essential to understand limb growth and pattern formation, as the development of its areas proceeds simultaneously.

Expression of sonic hedgehog signaling pathways in a rat model of chronic pancreatitis

To establish a rat model of chronic pancreatitis, and to prove the activation of sonic hedgehog [SHH] signaling pathways in chronic pancreatitis. This study was conducted between January and July 2008 in the Department of General Surgery, Wuhan General Hospital, Guangzhou Military Command, Wuhan, China. Thirty Wistar rats were randomly divided into 3 groups: control group [A], experimental control group [B], and model group [C] [10 rats in each group]. Trinitrobenzene sulfonic acid was infused into the pancreatic duct to induce chronic pancreatitis in the model group rats. In the experimental control group, we opened the abdominal cavity and infused with 0.9% sodium chloride solution. Serum levels of bilirubin and amylase were determined by radioimmunoassay. Histopathological alterations were studied using the optical microscopy. Expression of patched-1 [PTCH-1], smoothened [SMO], and SHH were detected by immunohistochemistry. Compared with the control group [A], the serum bilirubin and amylase in the model group increased significantly after 7 days of treatment, and fibrotic proliferation of pancreatic tissues were found after 35 days; the expression of PTCH-1, SMO, and SHH in the pancreatic tissue increased significantly in the model group. Trinitrobeneze sulfonic acid can induce chronic pancreatitis in rat. The SHH signaling pathway is activated in rats with chronic pancreatitis