Merkwitz Claudia, Lochhead Paul, Tsikolia Nika, Koch Daniela, Sygnecka Katja, Sakurai Michiharu, Spanel-Borowski Katharina, Ricken Albert M
Institute of Anatomy, University of Leipzig, Liebigstraße 13, 04103 Leipzig, Germany.
Prog Histochem Cytochem. 2011 Nov;46(3):131-84. doi: 10.1016/j.proghi.2011.09.001. Epub 2011 Oct 2.
KIT is a type III receptor protein tyrosine kinase, and KITL its cognate ligand. KIT can mediate its effects via several intracellular signalling pathways, or by formation of a cell-cell anchor with its ligand. Through these mechanisms, KIT controls fundamental cellular processes, including migration, proliferation, differentiation and survival. These cellular processes are modulated by soluble KIT, a cleavage product of KIT, generated at the cell membrane. A cell-retained KIT cleavage fragment also arises from this cleavage event. This cleavage fragment must be distinguished from truncated KIT (trKIT), which originates through cryptic promoter usage. The expression of trKIT is highly restricted to postmeiotic germ cells in the testis. In contrast, KIT, together with its cleavage products, is present in somatic cells and germ cells in the gonads of both sexes. A functional KITL/KIT system is mandatory for normal population of the gonads by germ cells. Signalling via the KITL/KIT system promotes the growth, maturation, and survival of germ cells within the gonads, and prevents meiotic entry and progression. In addition to its importance in germ cell biology, the KITL/KIT system is crucial for gonadal stromal differentiation. During foetal life, KIT is expressed by testicular stromal precursor cells, which develop into Leydig cells. In the ovary, stromal cell KIT expression accompanies theca layer development around advanced follicles. After ovulation, KIT-immunopositive cells translocate from the theca layer to the luteal ganulosa where they contribute to a delicate cellular network that extends between the fully luteinised large luteal cells. In the outer regions of the developing corpus luteum, a highly conspicuous subpopulation of KIT/CD14-double-immunopositive cells can be observed. KIT/CD14-double-immunopositive cells are also seen in the haematopoietic-like colonies of long-term granulosa cultures established from late antral follicles. These cultures demonstrate expression of pluripotency marker genes such as octamer binding transcription factor-3/4 and sex determining region Y-box 2. The KIT/CD14-double-immunopositive cells can be purified and enriched by KIT-immunopositive magnetic cell sorting. Subsequent exposure of the KIT-expressing cells to the hanging drop culture method, combined with haematopoietic differentiation medium, provides the signals necessary for their differentiation into endothelial and steroidogenic cells. This suggests that monocyte-derived multipotent cells are involved in ovarian tissue remodelling. In summary, multicelluar KITL/KIT signalling organizes the stroma in the ovary and testis; monocyte-derived multipotent cells may be involved.
KIT是一种III型受体蛋白酪氨酸激酶，而KITL是其同源配体。KIT可通过多种细胞内信号通路介导其作用，或通过与其配体形成细胞 - 细胞锚定来发挥作用。通过这些机制，KIT控制着包括迁移、增殖、分化和存活在内的基本细胞过程。这些细胞过程受到可溶性KIT的调节，可溶性KIT是KIT在细胞膜上产生的一种裂解产物。细胞保留的KIT裂解片段也源于这一裂解事件。这种裂解片段必须与截短的KIT（trKIT）区分开来，trKIT是通过隐秘启动子的使用而产生的。trKIT的表达高度局限于睾丸中的减数分裂后生殖细胞。相比之下，KIT及其裂解产物存在于两性性腺的体细胞和生殖细胞中。功能性的KITL/KIT系统对于生殖细胞正常定殖于性腺是必不可少的。通过KITL/KIT系统的信号传导促进性腺内生殖细胞的生长、成熟和存活，并阻止减数分裂的进入和进程。除了在生殖细胞生物学中的重要性外，KITL/KIT系统对于性腺基质分化也至关重要。在胎儿期，KIT由睾丸基质前体细胞表达，这些细胞发育成Leydig细胞。在卵巢中，基质细胞KIT的表达伴随着成熟卵泡周围卵泡膜层的发育。排卵后，KIT免疫阳性细胞从卵泡膜层转移到黄体颗粒层，在那里它们形成一个精细的细胞网络，延伸于完全黄体化的大黄体细胞之间。在发育中的黄体的外部区域，可以观察到一个高度明显的KIT/CD14双免疫阳性细胞亚群。在从晚期窦状卵泡建立的长期颗粒细胞培养物的造血样集落中也可见到KIT/CD14双免疫阳性细胞。这些培养物显示出多能性标记基因如八聚体结合转录因子-3/4和性别决定区Y盒2的表达。KIT/CD14双免疫阳性细胞可以通过KIT免疫阳性磁性细胞分选进行纯化和富集。随后将表达KIT的细胞暴露于悬滴培养法，并结合造血分化培养基，为它们分化为内皮细胞和类固醇生成细胞提供必要的信号。这表明单核细胞来源的多能细胞参与了卵巢组织重塑。总之，多细胞的KITL/KIT信号传导组织了卵巢和睾丸中的基质；单核细胞来源的多能细胞可能参与其中。
