A study of the primordial germ cells during their migratory phase in steel mutant mice

McCoshen, John A.; McCallion, D. J.

doi:10.1007/bf01932475

Cited by 149 publications

(67 citation statements)

References 7 publications

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“…Furthermore, transmembrane SCF is more potent than soluble SCF in maintaining the survival of multipotent hemopoietic stem cells in vitro (48). Experiments in Sl/Sl d mouse embryos (48)(49)(50) have shown that, while transmembrane SCF plays a critical role in the proliferative response of primordial germ cells, soluble SCF is able to sustain cell migration but not cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes

Bellone¹,

Smirne²,

Carbone³

et al. 2006

Int J Oncol

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Abstract. Autocrine/paracrine stimulation of KIT has been observed in colorectal carcinoma (CRC) cell lines. We investigated the expression of KIT and stem cell factor (SCF) in CRC in comparison with premalignant colon lesions and normal colonic mucosa to assess the prognostic and therapeutic relevance of this receptor/ligand system in CRC. Transcript levels of c-kit and the two SCF splicing variants were determined quantitatively by real-time RT-PCR using cDNA obtained from normal, premalignant and malignant snap frozen colon tissue specimens. Immunohistochemistry with specific anti-KIT and anti-SCF antibodies was performed on paraffin-embedded tissue sections in order to localize the relative protein expression in epithelial compartments. Approximately 10% of patients expressed KIT in their adenoma or primary tumor. The majority of KIT-positive carcinomas co-expressed SCF. Real-time RT-PCR showed expression of c-kit and SCF transcripts in all cDNA specimens examined. A significant association between the co-expression of KIT/SCF and a worse clinical outcome was found. In conclusion, KIT expression was observed in a proportion of premalignant and malignant colonic lesions, while it was virtually absent in normal colon mucosa. Moreover, the majority of KIT-positive carcinomas co-expressed SCF, suggesting the possibility of aberrant signaling by an autocrine loop, as confirmed by the negative prognostic value of this association. Therefore, in the subset of CRC patients with concomitant KIT/SCF expression, the activity of Imatinib mesylate, a selective inhibitor of specific tyrosine kinases including KIT, may be exploited in combination with standard therapy.

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Section: Discussionmentioning

confidence: 99%

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes

Bellone¹,

Smirne²,

Carbone³

et al. 2006

Int J Oncol

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“…Disruption of the Kit receptorlligand interaction by injection of monoclonal antibodies against the c-kit gene product also suggests that this receptor is necessary postnatally for melanocyte activation . Studies on the role of c-kit in germ cell development has also provided evidence that a functional Kit1 Steel factor signalling pathway is necessary both for the survival of early germ cells during their migration toward the genital ridges and for postnatal development of germ cells (Bennett, 1956;Mintz and Russell, 1957;McCoshen and McCallion, 1975). Evidence in support of a postnatal role include the observations that SIISlt newborn ovaries contain numerous oocytes which fail to develop beyond the primordial follicular stage ; germ cells in Sll+ adults show impaired differentiation in artificial cryptorchidism and organ culture (Nishimune et al, 1980(Nishimune et al, , 1984; and type A spermatogonia are blocked in mitosis after injection of monoclonal antibodies against the Kit receptor into prepubertal mice .…”

Section: Introductionmentioning

confidence: 99%

Dynamic changes in ovarian c‐kit and Steel expression during the estrous reproductive cycle

Motro

Bernstein

1993

Developmental Dynamics

123

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Wand Steel mutant mice exhibit similar developmental defects in melanogenesis, haematopoiesis, and gametogenesis. Consistent with the cell autonomous and microenvironmental nature of W and S Z mutations, respectively, W encodes the c-kit receptor tyrosine kinase while Steel enclodes the Kit ligand. Both c-kit and Steel are expressed in various cells in which no corresponding mutant phenotype has yet been demonstrated. In the adult ovary, certain stromal-derived cells (theca and interstitial), as well as oocytes, express c-kit, while granulosa cells express Steel. We show here that the cessation of oocyte growth, at the transition of the follicle to the antral stage, is associated with the cessation of Steel expression in the cumulus granulosa cells in the vicinity of the oocyte. These observations suggest a role for the Kit signaling pathway in oocyte growth or in meiotic arrest. In addition, the cyclic secretion of luteinizing hormone immediately and dramatically results in elevated Steel expression in mural granulosa cells and decreased levels of c-kit transcripts in stromal-derived cells. This influence of the estrous reproductive cycle on c-kit/ Steel expression suggests that the Kit signaling pathway, in addition to its previously described role in primordial germ cell development, is involved in follicular development in the adult female. 0 1993 Wiley-Liss, Inc.

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“…1; Richardson and Lehmann, 2010). Fertility in the adult relies upon the successful migration of the germline; failure to complete this process results in a loss of functional germ cells and increased risk for the development of germ cell tumors (Mintz and Russell, 1957;McCoshen and McCallion, 1975;Chaganti et al, 1994). Through the study of multiple model organisms, it has been shown that the overall process of PGC migration -interaction with multiple tissue types, receptivity to and sensing of chemoattractant and repellant cues -is highly conserved, and several key genes and signaling pathways have been identified (Richardson and Lehmann, 2010).…”

Section: Conservation Of Primordial Germ Cell Migrationmentioning

confidence: 99%

“…The best characterized ligandreceptor pair in PGC migration is KitL (also known as Steel factor or Stem cell factor) and cKit. Early studies of mice carrying mutations in the cKit locus (also known as W) or KitL locus (also known as Steel) noted a dramatic reduction in population size of the germline as well as a delay in the migration of PGCs that resulted in failure to efficiently colonize the gonadal ridges (Mintz and Russell, 1957;McCoshen and McCallion, 1975;Buehr et al, 1993;Runyan et al, 2006). Careful characterization of KitL, which has both membranebound and secreted forms (Flanagan et al, 1991;Huang et al, 1992;Miyazawa et al, 1995), revealed its expression by somatic cells of the embryonic mesoderm and gonadal ridges to be spatially and temporally dynamic along the migratory route, creating a wave of expression coined the "traveling niche" (Gu et al, 2009).…”

Section: Pgc Migration In the Mousementioning

confidence: 99%

“…Distinct from other model organisms (Su et al, 1998;Richardson and Lehmann, 2010;de Melo Bernardo et al, 2012), mammalian PGCs are actively proliferating during their migration, increasing in population size from approximately 45 cells at E7.5 to ~200 at E9.5 (Saitou et al, 2002;McLaren, 2003;Seki et al, 2007), ~2500 at E11.5 (Laird et al, 2011), and peaking around 25,000 at E13.5 (Tam and Snow, 1981). The KitL-cKit pathway is one regulator of germ cell proliferation, with several genetic mutants for either ligand or receptor unable to expand their number of PGCs after specification, resulting in fertility defects (Mintz and Russell, 1957;McCoshen and McCallion, 1975;Buehr et al, 1993). Adding to its functions as a mitogen and chemoattractant, KitL has also been shown to play a role in PGC survival (Runyan et al, 2006).…”

Section: Other Key Cellular Processes During the Migratory Period In mentioning

confidence: 99%

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Primordial germ cell migration and the Wnt signaling pathway

Cantu

Laird

2017

Anim Reprod

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A critical step in the development of gametes is the migration of their primordial germ cell (PGC) precursors to the forming gonads. Although the location and mode of PGC specification differs between organisms, the formation of a committed germline before organogenesis creates a need for migration through the growing embryo in order to reach the site of gonadogenesis. Failure of PGC migration can, in many cases, compromise fertility or conversely lead to the formation of teratomas in sites outside of the gonad. Here we review the mechanism of migration employed by PGCs and compare the timing and routes across several model organisms. We summarize recent work on the role of the Wnt signaling pathway in cell migration and the lineage specific function in PGCs, mainly through the ligand Wnt5a and its receptor Ror2.

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A study of the primordial germ cells during their migratory phase in steel mutant mice

Cited by 149 publications

References 7 publications

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes

Dynamic changes in ovarian c‐kit and Steel expression during the estrous reproductive cycle

Primordial germ cell migration and the Wnt signaling pathway

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