The distribution and behavior of extragonadal primordial germ cells in Bax mutant mice suggest a novel origin for sacrococcygeal germ cell tumors.
In the mouse, germ cells that do not reach the genital ridges rapidly die by a wave of apoptosis that requires the pro-apoptotic protein Bax. In Bax-null embryos, large numbers of ectopic (extragonadal) germ cells fail to die. We have studied the fates of these, in an effort to understand the etiology of human extragonadal germ cell tumors, which are thought to arise from ectopic germ cells. We find that ectopic germ cells in which apoptosis is blocked form a heterogeneous population, which partially differentiates along the gonocyte pathway to different extents in different regions of the embryo, and in the two genders. In particular, a previously undescribed population of ectopic germ cells was identified in the tail. These germ cells retained primitive markers for longer than ectopic germ cells in other regions, and represent a possible origin for sacrococcygeal type I extragonadal germ cell tumors found in neonates and infants. This hypothesis is supported, but not proved, by the finding of cells expressing the germ cell marker Oct4 associated with a coccygeal germ cell tumor in a human infant.
Runyan
Christopher
C
Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
Gu
Ying
Y
Shoemaker
Amanda
A
Looijenga
Leendert
L
Wylie
Christopher
C
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002465:Cell Movement; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D005865:Gestational Age; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016256:Lewis X Antigen / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009373:Neoplasms, Germ Cell and Embryonal / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012445:Sacrococcygeal Region; D051028:bcl-2-Associated X Protein / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
C494827:Bax protein, mouse; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D016256:Lewis X Antigen; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011993:Recombinant Fusion Proteins; C490062:Sycp3 protein, mouse; D051028:bcl-2-Associated X Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C090864:Ddx4 protein, mouse; D053487:DEAD-box RNA Helicases