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Functional Assessment of Kinesin-7 CENP-E in Spermatocytes Using In Vivo Inhibition, Immunofluorescence and Flow Cytometry
Published on: December 28, 2021
Molecular mechanisms utilized by alternative c-kit gene products in the control of spermatogonial proliferation and
1Dipartimento di Sanita' Pubblica e Biologia Cellulare, Sezione di Anatomia, Universita' degli Studi di Roma Tor Vergata, Rome, Italy. pellegrino.rossi@med.uniroma2.it
Abstract:
The c-kit proto-oncogene plays a dual role in the control of male fertility in mice through two alternative gene products: (1). c-kit [the transmembrane tyrosine kinase receptor for stem cell factor (SCF)], which is expressed and functional in differentiating spermatogonia of the postnatal testis, in which c-kit is essential for pre-meiotic proliferation; and (2). tr-kit, an intracellular protein which is specifically accumulated during spermiogenesis through the use of an alternative intronic promoter, and which is able to trigger mouse egg activation when microinjected into the cytoplasm of metaphase II arrested oocytes. Here, we summarize the most recent findings about the molecular pathways through which c-kit regulates cell cycle progression in mitotic germ cells, and those through which sperm-derived tr-kit triggers parthenogenetic completion of meiosis II and pronuclear formation in microinjected mouse eggs.
Insights
The c-kit proto-oncogene has two forms: c-kit, vital for male germ cell proliferation, and tr-kit, which triggers egg activation. This research explores their roles in male fertility and reproduction.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Cell Biology
Background:
- The c-kit proto-oncogene encodes two distinct proteins through alternative gene products.
- c-kit is a transmembrane tyrosine kinase receptor for stem cell factor (SCF).
- tr-kit is an intracellular protein product of the c-kit gene.
Purpose of the Study:
- To summarize recent findings on the molecular pathways of c-kit in male germ cell proliferation.
- To elucidate the mechanisms by which sperm-derived tr-kit induces egg activation and completion of meiosis.
- To highlight the dual role of the c-kit proto-oncogene in male fertility and reproduction.
Main Methods:
- Review of recent molecular and cellular biology findings.
- Analysis of gene expression and protein accumulation during spermatogenesis.
- Microinjection experiments of tr-kit into mouse oocytes.
Main Results:
- c-kit is essential for the proliferation of spermatogonia in the postnatal mouse testis.
- tr-kit accumulates during spermiogenesis via an alternative intronic promoter.
- Microinjected tr-kit triggers parthenogenetic completion of meiosis II and pronuclear formation in mouse eggs.
Conclusions:
- The c-kit proto-oncogene plays a critical dual role in male fertility.
- c-kit regulates mitotic germ cell cycle progression.
- tr-kit initiates key events in oocyte activation, essential for reproduction.
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Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...

