Quantitative Histology of Spleen Colonies in Irradiated Mice

Silini, G.; Pons, S; Pozzi, Laura

doi:10.1111/j.1365-2141.1968.tb07000.x

Cited by 40 publications

(12 citation statements)

References 13 publications

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“…As shown in Fig. 1 (26,27). Since only the hepatocytes contribute to AFP mRNA and albumin mRNA synthesis, at least part of the increase in the tissue concentrations of AFP mRNA before birth and albumin mRNA both before and after birth can be attributed to this factor.…”

Section: Resultsmentioning

confidence: 94%

“…By 7 days after birth, nascent AFP mRNA can be detected only by exposing the blot for two weeks (lane B') and, at later ages, no AFP-specific RNA is detected. It is not possible to compare absolute rates of transcription for each gene at different stages, as the fetal liver at 20 days is still comprised of only 40% hepatocytes and this percentage increases throughout the early postnatal period to =75% by 4 wk (26,27). Instead, the AFP-specific/ albumin-specific transcription ratio was calculated for each developmental stage from densitometric scans of several exposures ofthe autoradiogram (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Transcriptional control of the murine albumin/alpha-fetoprotein locus during development.

Tilghman¹,

Belayew²

1982

Proc. Natl. Acad. Sci. U.S.A.

327

221

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The ontogeny of expression of the a-fetoprotein (AFP) and albumin genes was examined in livers from late prenatal to 1-month-postpartum C3H/He mice. A parallel accumulation of both AFP and albumin mRNAs before birth, followed by a selective nonreciprocal decrease in AFP mRNA after birth, was observed. The decrease in AFP mRNA was the result of a decrease in transcription of the AFP gene, as measured by an in vitro nuclear transcription assay. We suggest a model for hepatic expression of the AFP and albumin gene cluster in which transcription ofthe two genes is activated simultaneously during differentiation and each gene is thereafter modulated independently in committed cells.The a-fetoprotein (AFP) and albumin genes, which code for the major mammalian fetal and adult serum proteins, respectively, arose in evolution as the consequence of a duplication of an ancestral gene, 300-500 million years ago (1-6). Since that time, the murine genes have remained closely linked in tandem on chromosome 5, with the 3' terminus of the albumin gene 13.5 kilobases (kb) ofDNA to the 5' side of the AFP gene (7,8). The selective advantage to the organism for maintaining these genes in close proximity over such a long time span may reside in the development of cis-acting regulatory mechanisms that govern the expression of both genes during development. Such a mechanism has been hypothesized for the switch in the synthesis of human fetal y-globin to adult ,3-globin chains, based on the apparent requirement of DNA sequences downstream of the y-globin genes for the postnatal persistence of y-globin synthesis in certain thalassemia syndromes (9)(10)(11). As yet, there are no other known examples to provide evidence as to the generality of this type of coupled regulation of linked genes.However, the ontogeny ofthe expression ofthe murine AFP and albumin genes in the developing liver, previously examined by using cell-free translation ofmRNA (12), suggested that there is a-reciprocal relationship between the concentrations of the two RNAs akin to that observed for human 'y-and ,3-globin mRNAs. In the study reported in this paper, we used the more direct method of hybridization to measure the concentrations ofAFP and albumin mRNAs in the mouse liver during pre-and postnatal development. Rather than a strict reciprocal switch in their concentrations, we observe a parallel accumulation of both RNAs early in development followed by a selective decrease in AFP mRNA at birth. Furthermore, we show that transcriptional modulation is the primary molecular mechanism underlying the decrease in AFP mRNA after birth. MATERIALS AND METHODS 5254The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Transcriptional control of the murine albumin/alpha-fetoprotein locus during development.

Tilghman¹,

Belayew²

1982

Proc. Natl. Acad. Sci. U.S.A.

327

221

View full text Add to dashboard Cite

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“…Much of this increase appears to be due to faster transcription of already active genes during late stages of development (36). These measurements on fetal liver may reflect an increase in hepatocytes and a decrease in hematopoietic cells during development, but this change in cell composition is no more than a factor of 2 to 3 (35,41), whereas the changes in mRNA and transcription approach or exceed a factor of 10. Thus it seems possible that already differentiated fetal hepatocytes as they mature do increase the frequency of transcription of liver-specific RNAs.…”

Section: Discussionmentioning

confidence: 96%

Dependence of liver-specific transcription on tissue organization.

1985

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When the liver is disaggregated and hepatocytes are cultured as a cellular monolayer for 24 h, a sharp decline (80 to 99% decrease) in the transcription of most liver-specific mRNAs, but not common mRNAs, occurs (Clayton and Darnell, Mol. Cell. Biol. 2:1552-1561. A wide variety of culture conditions involving various hormones and substrates and cocultivation with other cells failed to sustain high rates of liver-specific mRNA synthesis in cultured hepatocytes, although they continued to synthesize common mRNAs at normal or elevated rates. In contrast, when slices of intact mouse liver tissue were placed in culture, the transcription of liver-specific genes was maintained at high levels (20 to 100% of normal liver). Furthermore, we found that cells in the liver could be disengaged and immediately reengaged in a tissue-like structure by perfusing the liver with EDTA followed by serum-containing culture medium. Slices of reengaged liver continued to transcribe tissue-specific mRNA sequences at significantly higher rates after 24 h in culture than did individual cells isolated by EDTA perfusion followed by culturing as a monolayer. Therefore we conclude that a mature tissue structure plays an important role in the maintenance of maximum tissue-specific transcription in liver cells.

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“…Only spleens that contained a number of macroscopic colonies comparable to those enumerated by surface counting were examined microscopically. Spleen colony composition was analyzed according to the method of Silini et al (19) and three to four spleens were evaluated for each experimental point. Tritiated thymidine suicide studies (1,20 Reagents.…”

Section: Methodsmentioning

confidence: 99%