The Role of Neurogenin 3 in Pancreas Development

描述：Ngn 3（神经生成素3）是一种bHLH转录因子，表达于 胰腺内分泌前体细胞。Ngn 3 mRNA在发育中的 胰腺在妊娠第9天至第18.5天之间。ngn 3的表达是 在分化的胰岛α和β细胞中消失，因为它从来没有 与胰高血糖素或胰岛素共定位。Ngn 3的纯合子无效小鼠发育 严重的糖尿病，出生后2-3天死亡。没有哪个朗格汉斯岛 存在于这些突变动物的胰腺中。因此，Ngn 3绝对是 对胰腺内分泌细胞发育至关重要，也是 内分泌前体细胞的最早标志物。以下具体目标将 1）通过同源重组产生Ngn 3-GFP小鼠， 重组用于谱系追踪研究和用于纯化， 培养内分泌干细胞。 2)利用基因芯片技术鉴定Ngn 3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.