Manova K, Huang E J, Angeles M, De Leon V, Sanchez S, Pronovost S M, Besmer P, Bachvarova R F
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, New York 10021.
Dev Biol. 1993 May;157(1):85-99. doi: 10.1006/dbio.1993.1114.
The tyrosine kinase receptor c-kit and its ligand KL are required for postnatal development of germ cells, in addition to their role in primordial germ cells. To clarify their function, a detailed examination of the pattern of expression of KL in postnatal gonads was undertaken. In ovaries, the expression of KL as seen by RNA blot analysis and by RNase protection assays is relatively high at birth (P0), low from P5 to P8, and high from P12 onward. KL expression is relatively high in testes of all ages. The forms of KL RNA present in the testes suggest that from P5 onward the membrane-bound form of KL predominates, while in the ovary significant amounts of both forms are present. As observed by in situ hybridization and immunohistochemistry, in the newborn ovary KL is highly expressed in central cords whose cells contribute to the formation of central growing follicles. Expression is low in follicle cells of small growing follicles and increases to high levels in three-layered follicles during late oocyte growth. Large amounts of the ligand are found within growing oocytes. After oocyte growth ceases, expression continues only in the outer layers of multilayered follicles. In the testis, from P0 through P9, KL expression is distinct in Sertoli cells, but not in germ cells. Thereafter, the intensity of KL expression declines as the number of spermatogenic cells increases within the tubules. KL in Sertoli cells appears to be concentrated basally at the stage of the cycle of the seminiferous epithelium when it is known to interact with differentiating type A spermatogonia. These data are consistent with a role for KL in oocyte growth and in facilitating proliferation and/or differentiation of type A spermatogonia.
酪氨酸激酶受体c-kit及其配体KL除了在原始生殖细胞中发挥作用外,对出生后生殖细胞的发育也是必需的。为了阐明它们的功能,我们对出生后性腺中KL的表达模式进行了详细研究。在卵巢中,通过RNA印迹分析和核糖核酸酶保护试验观察到,KL的表达在出生时(P0)相对较高,在P5至P8时较低,从P12起又升高。在所有年龄段的睾丸中,KL的表达都相对较高。睾丸中存在的KL RNA形式表明,从P5起,KL的膜结合形式占主导,而在卵巢中,两种形式都大量存在。通过原位杂交和免疫组织化学观察发现,在新生卵巢中,KL在中央索中高度表达,中央索中的细胞有助于中央生长卵泡的形成。在小生长卵泡的卵泡细胞中表达较低,在卵母细胞生长后期的三层卵泡中表达增加到高水平。在生长中的卵母细胞内发现大量配体。卵母细胞生长停止后,表达仅在多层卵泡的外层继续。在睾丸中,从P0到P9,KL在支持细胞中表达明显,但在生殖细胞中不表达。此后,随着生精细胞在小管内数量的增加,KL的表达强度下降。支持细胞中的KL似乎在生精上皮周期的这个阶段集中在基部,此时已知它与分化型A精原细胞相互作用。这些数据与KL在卵母细胞生长以及促进A型精原细胞的增殖和/或分化中的作用一致。