The Role of Neurogenin 3 in Pancreas Development

描述：NGN3(Neurogenin 3)是一种bHLH转录因子，在 胰腺内分泌前体细胞。NGN3基因在发育过程中被发现 胰腺在妊娠第9天至18.5天之间。NGN3的表达是 在分化的胰岛α和β细胞中熄灭，因为它永远不会 与胰高血糖素或胰岛素共定位。Ngn3纯合子缺失小鼠发育 严重糖尿病，出生后2-3天死亡。没有一座朗格汉岛是 存在于这些突变动物的胰腺中。因此，Ngn3绝对是 对胰腺内分泌细胞发育是必不可少的，它也是 内分泌前体细胞的最早标记。以下具体目标将 通过这一建议：1)通过同源基因获得Ngn3-GFP小鼠 重组用于谱系追踪研究和用于纯化和 内分泌干细胞的培养。2)利用基因芯片技术筛选Ngn3的早期和晚期靶基因。

DESCRIPTION: Ngn3 (neurogenin 3) is a bHLH transcription factor expressed in the pancreatic endocrine precursor cells. Ngn3 mRNA is found in the developing pancreas between day 9 and 18.5 of gestation. Expression of ngn3 is extinguished in differentiated islet alpha and beta cells, as it never co-localizes with glucagon or insulin. Homozygous null mice for Ngn3 develop severe diabetes and die 2-3 days after birth. No islet of Langerhans are present in the pancreas in these mutant animals. Thus, Ngn3 is absolutely essential for the pancreatic endocrine cell development and it is also the earliest marker for endocrine precursor cells. The following specific aims will be pursued through this proposal: 1) To generate a Ngn3-GFP mouse by homologous recombination to be used in lineage tracing study and for the purification and culture of endocrine stem cells. 2) To identify early and late target genes of Ngn3 using microarray technology.