Wilson Maria E, Yang Katherine Y, Kalousova Anna, Lau Janet, Kosaka Yasuhiro, Lynn Francis C, Wang Juehu, Mrejen Caroline, Episkopou Vasso, Clevers Hans C, German Michael S
Diabetes Center, Hormone Research Institute, University of California at San Francisco, 513 Parnassus Ave., San Francisco, California 94143-0534, USA.
Diabetes. 2005 Dec;54(12):3402-9. doi: 10.2337/diabetes.54.12.3402.
To investigate the role of the Sry/hydroxymethylglutaryl box (Sox) transcription factors in the development of the pancreas, we determined the expression pattern of Sox factors in the developing mouse pancreas. By RT-PCR, we detected the presence of multiple Sox family members in both the developing pancreas and mature islets and then focused on two factors, Sox2 and Sox4. The expression field of Sox2, which plays a role in the maintenance of some stem cell populations, included the developing duodenum, but Sox2 was specifically excluded from the pancreatic buds. In contrast, Sox4 was detected broadly in the early pancreatic buds and eventually became restricted to the nuclei of all islet cells in the adult mouse. Mice homozygous for a null mutation of the sox4 gene showed normal pancreatic bud formation and endocrine cell differentiation up to embryonic day 12.5. Beyond that date, cultured pancreatic explants lacking sox4 failed to form normal islets. Instead, a markedly reduced number of endocrine cells were found scattered through the explant. We show here that several Sox transcription factors are expressed in the developing pancreas and in the islet, and that one of these factors, Sox4, is required for the normal development of pancreatic islets.
为了研究Sry/羟甲基戊二酰辅酶A盒（Sox）转录因子在胰腺发育中的作用，我们确定了Sox因子在发育中的小鼠胰腺中的表达模式。通过逆转录聚合酶链反应（RT-PCR），我们在发育中的胰腺和成熟胰岛中均检测到多个Sox家族成员的存在，随后重点研究了两个因子，即Sox2和Sox4。在维持某些干细胞群体方面发挥作用的Sox2，其表达区域包括发育中的十二指肠，但胰腺芽中特意没有Sox2。相反，Sox4在早期胰腺芽中广泛表达，最终在成年小鼠中局限于所有胰岛细胞的细胞核。Sox4基因无效突变的纯合子小鼠在胚胎第12.5天之前胰腺芽形成和内分泌细胞分化均正常。在该时间点之后，缺乏Sox4的培养胰腺外植体无法形成正常胰岛。相反，在外植体中发现散在分布的内分泌细胞数量明显减少。我们在此表明，几种Sox转录因子在发育中的胰腺和胰岛中表达，并且其中一个因子Sox4是胰岛正常发育所必需的。
