Alpha-防御素
中文名称
通路描述
人类有 7 个 Alpha-防御素基因及 5 个假基因（参见 HGNC 网站）。Alpha-防御素含有六个通过 1-6、2-4、3-5 连接的半胱氨酸。人类 Alpha-防御素的典型序列为 x1-2CXCRx2-3Cx3Ex3GxCx3Gx5CCx1-4，其中 x 代表任何氨基酸残基。人类 Alpha-防御素 1-4 最初在中性粒细胞初级（嗜天青颗粒）中鉴定，常被称为人类中性粒细胞肽（HNP1-4）。Alpha-防御素 5 和 6（HD5、HD6）是潘氏细胞的产物。HNP-1 和 -3 肽段长 30 个氨基酸，仅第一个氨基酸不同，分别由 DEFA1 和 DEFA3 基因编码。这些肽段存在拷贝数多态性，某些个体每个二倍体基因组中有 4-14 个拷贝，而 10-37% 的个体没有 DEFA3 的拷贝。HNP-4 由 DEFA4 编码，长 33 个氨基酸，其中 22 个与其他 HNP 不同，是中性粒细胞颗粒中的次要成分。与 DEFA1 和 DEFA3 不同，HNP-4、HD-5 和 HD-6 的基因仅在二倍体基因组中存在两个拷贝。HNP-2 长 29 个氨基酸，是 HNP-1 和/或 HNP-3 的 N 端氨基酸被蛋白酶切割后的产物。
英文描述
Formation of paraxial mesoderm Skeletal tissues originate from paraxial mesoderm, lateral plate mesoderm, and neural crest. Paraxial mesoderm is produced by invagination of cells through the primitive streak and is the precursor of somites, which are spheres of mesenchyme bounded by epithelium that bud at fixed intervals from the anterior paraxial mesoderm in a process termed somitogenesis (reviewed in Tam and Trainor 1994, Pourquie 2003). Somites give rise to the axial skeleton and skeletal muscles.
Paraxial mesoderm becomes specified at a lower level of BMP signaling (Xi et al. 2017) that results from the interaction of BMP4, produced by the lateral plate mesoderm, with NOGGIN (NOG), a negative regulator of BMP signaling produced by the notochord (reviewed in Tani et al. 2020). WNT signaling by WNT3A that activates betaâcatenin (CTNNB1), FGF signaling that acts though FGFR1, and TBXT activate expression of TBX6 and Mesogenin 1 (MSGN1). MSGN1 binds and activates SNAI1 to promote epithelial-mesenchymal transitions (EMT). TBX6 activates MSGN1, and MSGN1 activates TBX6, to establish a positive feedback loop that ensures commitment to the paraxial mesoderm lineage. TBX6 and MSGN1 act with WNT signaling to activate expression of MSGN1, and the NOTCH ligand Deltaâlike 1 (DLL1), which enhances NOTCH signaling. MSGN1 binds and activates expression of DLL1, DLL3, NOTCH1, and NOTCH2, and binds to Clock enhancers that regulate periodic expression of LFNG during somitogenesis in the anterior paraxial mesoderm. The counterbalancing DLL3 protein inhibits NOTCH signaling by binding NOTCH1 in endosomes and targeting NOTCH1 for lysosomal degradation.
TBX6 alone is capable of reprogramming pluripotent stem cells to paraxial mesoderm (Sadahiro et al. 2018) and acts in a regulatory loop with MESP2 to create the boundaries of nascent somites (Oginuma et al. 2011): TBX6 activates expression of MESP2 which then represses TBX6 by targeting TBX6 for degradation, leaving MESP2 alone at the segmental boundary.
Paraxial mesoderm becomes specified at a lower level of BMP signaling (Xi et al. 2017) that results from the interaction of BMP4, produced by the lateral plate mesoderm, with NOGGIN (NOG), a negative regulator of BMP signaling produced by the notochord (reviewed in Tani et al. 2020). WNT signaling by WNT3A that activates betaâcatenin (CTNNB1), FGF signaling that acts though FGFR1, and TBXT activate expression of TBX6 and Mesogenin 1 (MSGN1). MSGN1 binds and activates SNAI1 to promote epithelial-mesenchymal transitions (EMT). TBX6 activates MSGN1, and MSGN1 activates TBX6, to establish a positive feedback loop that ensures commitment to the paraxial mesoderm lineage. TBX6 and MSGN1 act with WNT signaling to activate expression of MSGN1, and the NOTCH ligand Deltaâlike 1 (DLL1), which enhances NOTCH signaling. MSGN1 binds and activates expression of DLL1, DLL3, NOTCH1, and NOTCH2, and binds to Clock enhancers that regulate periodic expression of LFNG during somitogenesis in the anterior paraxial mesoderm. The counterbalancing DLL3 protein inhibits NOTCH signaling by binding NOTCH1 in endosomes and targeting NOTCH1 for lysosomal degradation.
TBX6 alone is capable of reprogramming pluripotent stem cells to paraxial mesoderm (Sadahiro et al. 2018) and acts in a regulatory loop with MESP2 to create the boundaries of nascent somites (Oginuma et al. 2011): TBX6 activates expression of MESP2 which then represses TBX6 by targeting TBX6 for degradation, leaving MESP2 alone at the segmental boundary.
所含基因
23 个基因