Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo

Development ◽  
1991 ◽  
Vol 111 (1) ◽  
pp. 131-143 ◽  
Author(s):  
F.A. Millan ◽  
F. Denhez ◽  
P. Kondaiah ◽  
R.J. Akhurst
Keyword(s):  
Growth Factors ◽  
Developmental Process ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Tgf Beta ◽  
Genes Encoding ◽  
Beta 2 ◽  
Valve Formation

We have compared the expression of the genes encoding transforming growth factors beta 1, beta 2 and beta 3 during mouse embryogenesis from 9.5 to 16.5 days p.c. using in situ hybridisation to cellular RNAs. Each gene has a different expression pattern, which gives some indication of possible biological function in vivo. All three genes appear to be involved in chondroossification, though each is expressed in a different cell type. Transcripts of each gene are also present in embryonic epithelia. Epithelial expression of TGF beta 1, beta 2 and beta 3 RNA is associated with regions of active morphogenesis involving epithelial-mesenchymal interactions. In addition, widespread epithelial expression of TGF beta 2 RNA can be correlated with epithelial differentiation per se. The localisation of TGF beta 2 RNA in neuronal tissue might also be correlated with differentiation. Finally both TGF beta 1 and beta 2 transcripts are seen in regions actively undergoing cardiac septation and valve formation, suggesting some interaction of these growth factors in this developmental process.

Differential expression of TGF beta isoforms in murine palatogenesis

Development ◽  
1990 ◽  
Vol 109 (3) ◽  
pp. 585-595 ◽  
Author(s):  
D.R. Fitzpatrick ◽  
F. Denhez ◽  
P. Kondaiah ◽  
R.J. Akhurst
Keyword(s):  
Developmental Process ◽  
Biological Activities ◽  
In Situ Hybridisation ◽  
Tgf Beta ◽  
Temporal And Spatial Distribution ◽  
Palatal Shelf ◽  
Genes Encoding ◽  
Beta 2 ◽  
Medial Edge

We have studied the expression of genes encoding transforming growth factors (TGFs) beta 1, beta 2 and beta 3 during development of the secondary palate in the mouse from 11.5 to 15.5 days postcoitum using in situ hybridisation. The RNA detected at the earliest developmental stage is TGF beta 3, which is localised in the epithelial component of the vertical palatal shelf. This expression continues in the horizontal palatal shelf, predominantly in the medial edge epithelium, and is lost as the epithelial seam disrupts, soon after palatal shelf fusion. TGF beta 1 RNA is expressed with the same epithelial pattern as TGF beta 3, but is not detectable until the horizontal palatal shelf stage. TGF beta 2 RNA is localised to the palatal mesenchyme underlying the medial edge epithelia in the horizontal shelves and in the early postfusion palate. The temporal and spatial distribution of TGF beta 1, beta 2 and beta 3 RNAs in the developing palate, together with a knowledge of in vitro TGF beta biological activities, suggests an important role for TGF beta isoforms in this developmental process.

Differential expression of TGF beta 1, beta 2 and beta 3 genes during mouse embryogenesis

Development ◽  
1991 ◽  
Vol 111 (1) ◽  
pp. 117-130 ◽  
Author(s):  
P. Schmid ◽  
D. Cox ◽  
G. Bilbe ◽  
R. Maier ◽  
G.K. McMaster
Keyword(s):  
Fetal Liver ◽  
In Situ Hybridisation ◽  
Regulatory Elements ◽  
Northern Analysis ◽  
Tgf Beta ◽  
Mouse Embryogenesis ◽  
Root Sheath ◽  
Cell Layers ◽  
Beta 2

We have examined by Northern analysis and in situ hybridisation the expression of TGF beta 1, beta 2 and beta 3 during mouse embryogenesis. TGF beta 1 is expressed predominantly in the mesodermal components of the embryo e.g. the hematopoietic cells of both fetal liver and the hemopoietic islands of the yolk sac, the mesenchymal tissues of several internal organs and in ossifying bone tissues. The strongest TGF beta 2 signals were found in early facial mesenchyme and in some endodermal and ectodermal epithelial cell layers e.g., lung and cochlea epithelia. TGF beta 3 was strongest in prevertebral tissue, in some mesothelia and in lung epithelia. All three isoforms were expressed in bone tissues but showed distinct patterns of expression both spatially and temporally. In the root sheath of the whisker follicle, TGF beta 1, beta 2 and beta 3 were expressed simultaneously. We discuss the implication of these results in regard to known regulatory elements of the TGF beta genes and their receptors.

RNA and protein localisations of TGF beta 2 in the early mouse embryo suggest an involvement in cardiac development

Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 625-639 ◽  
Author(s):  
M.C. Dickson ◽  
H.G. Slager ◽  
E. Duffie ◽  
C.L. Mummery ◽  
R.J. Akhurst
Keyword(s):  
Cardiac Development ◽  
In Situ Hybridisation ◽  
Outflow Tract ◽  
Tgf Beta ◽  
Atrioventricular Canal ◽  
Whole Mount ◽  
Beta 2 ◽  
Low Levels ◽  
Early Mouse

We have performed a detailed analysis of the localisations of RNAs for TGF beta 2 and beta 3, and of TGF beta 2 protein in mouse embryos from 6.5 to 9.5 days post coitum, using in situ hybridisation and immunohistochemistry on serial sections, and whole-mount in situ hybridisation to complete embryos. TGF beta 3 RNA was not seen in any of the tissue sections, but very low levels of the RNA were seen by whole-mount in situ hybridisation around the outflow tract of the heart at 8.5 days post coitum. TGF beta 2 RNA is expressed at high levels in all cells with the potential to differentiate into cardiomyocytes. Additionally, the foregut endoderm, juxtaposed to the heart, and the neuroepithelium at the rostral extremity of the foregut, express very high levels of TGF beta 2 RNA, between 8.5 and 9.5 days post coitum. As cardiomyogenesis proceeds, TGF beta 2 RNA levels diminishes within the myocytes, with a concomitant increase in staining for TGF beta 2 protein. TGF beta 2 protein staining of cardiomyocytes persists throughout development and in the adult, in the absence of detectable levels of the corresponding RNA. Superimposed upon this myocardial pattern of expression, there is an upregulation of TGF beta 2 RNA in the myocardium of the outflow tract and atrioventricular canal between 8.5 and 9.5 days post coitum, which returns to low levels by 11.5 days post coitum. The results are discussed in terms of a potential role of TGF beta 2 in controlling cardiomyogenesis and in inductive interactions leading to cardiac cushion tissue formation.

Negative regulation of the P0 gene in Schwann cells: suppression of P0 mRNA and protein induction in cultured Schwann cells by FGF2 and TGF beta 1, TGF beta 2 and TGF beta 3

Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1399-1409 ◽  
Author(s):  
L. Morgan ◽  
K.R. Jessen ◽  
R. Mirsky
Keyword(s):  
Growth Factors ◽  
Cyclic Amp ◽  
Schwann Cells ◽  
Peripheral Nerves ◽  
Defined Medium ◽  
Complete Suppression ◽  
Tgf Beta ◽  
Beta 2

During the development of peripheral nerves, Schwann cells are induced to form myelin sheaths round the larger axons. This process involves a complex series of events and the nature of the molecular signals that regulate and control myelin formation in Schwann cells is not well understood. Our previous experiments on rat Schwann cells in vitro, using serum-free defined medium, showed that a myelin-related protein phenotype could be induced in early postnatal Schwann cells in culture by elevation of intracellular cyclic AMP levels in the absence of growth factors, conditions under which the cells are not dividing. Cells with this phenotype expressed the major myelin glycoprotein P0 and expression of p75 NGF receptor, N-CAM, GFAP and A5E3 proteins was down-regulated. These changes are all characteristics associated with myelination in vivo. In contrast, when cyclic AMP levels were elevated in the presence of serum, suppression of cyclic AMP-induced differentiation resulted and DNA synthesis was induced. In this paper, we have used this model system and extended our analysis to explore the relationship between defined growth factors and suppression of myelination. We have used pure recombinant growth factors normally present in peripheral nerves, i.e. FGF1 and FGF2 and TGF beta 1, TGF beta 2, and TGF beta 3 and shown that, like serum, they can strongly suppress the forskolin-mediated induction of the P0 gene, both at the level of mRNA and protein synthesis. For both growth factor families, the suppression of P0 gene expression is dose-dependent and takes place in serum-starved cells that are mitotically quiescent. In the case of FGF2, however, even more complete suppression is obtained when the cells are simultaneously allowed to enter the cell cycle by inclusion of high concentrations of insulin in the culture medium. The present results raise the possibility that, in addition to the positive axonal signals that are usually envisaged to control the onset of myelination, growth factors present in the nerve may exert negative regulatory signals during development and thus help control the time of onset and the rate of myelination in peripheral nerves.

Expression of TGF-beta isoforms during first trimester human embryogenesis

Development ◽  
1990 ◽  
Vol 110 (2) ◽  
pp. 445-460 ◽  
Author(s):  
D. Gatherer ◽  
P. Ten Dijke ◽  
D.T. Baird ◽  
R.J. Akhurst
Keyword(s):  
First Trimester ◽  
Human Embryos ◽  
Regulatory Sequences ◽  
Tgf Beta ◽  
Human Embryogenesis ◽  
Genes Encoding ◽  
Gene Regulatory ◽  
Beta 2 ◽  
Beta Gene

We have studied the expression of the genes encoding transforming growth factors (TGFs) beta 1, beta 2 and beta 3 in human embryos ranging from 32 to 57 days post-coitum, using in situ hybridization. The spatial and temporal pattern of expression of each gene is distinct, though each occasionally overlaps. TGF-beta 1 is expressed in haematopoietic, endothelial and osteogenic tissues. TGF-beta 2 and TGF-beta 3 are expressed in a wide variety of mesenchymal tissues including areas of chondrogenic activity. TGF-beta 2 is also found in several epithelial and in the ventral nervous system. The differential transcript distributions are broadly similar to those seen in mouse embryos suggesting that there is conservation of TGF-beta gene regulatory sequences and developmental function across this species boundary.

Complex regulation of TGF beta expression by retinoic acid in the vitamin A-deficient rat

Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 1081-1086 ◽  
Author(s):  
A.B. Glick ◽  
B.K. McCune ◽  
N. Abdulkarem ◽  
K.C. Flanders ◽  
J.A. Lumadue ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Alveolar Epithelium ◽  
Tgf Beta ◽  
Basal Expression ◽  
Beta 2 ◽  
Complex Regulation ◽  
First Time

We report the results of a histochemical study, using polyclonal antipeptide antibodies to the different TGF beta isoforms, which demonstrates that retinoic acid regulates the expression of TGF beta 2 in the vitamin A-deficient rat. Basal expression of TGF beta 2 diminished under conditions of vitamin A deficiency. Treatment with retinoic acid caused a rapid and transient induction of TGF beta 2 and TGF beta 3 in the epidermis, tracheobronchial and alveolar epithelium, and intestinal mucosa. Induction of TGF beta 1 expression was also observed in the epidermis. In contrast to these epithelia, expression of the three TGF beta isoforms increased in vaginal epithelium during vitamin A deficiency, and decreased following systemic administration of retinoic acid. Our results show for the first time the widespread regulation of TGF beta expression by retinoic acid in vivo, and suggest a possible mechanism by which retinoics regulate the functions of both normal and pre-neoplastic epithelia.

NeuroM, a neural helix-loop-helix transcription factor, defines a new transition stage in neurogenesis

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3263-3272 ◽  
Author(s):  
T. Roztocil ◽  
L. Matter-Sadzinski ◽  
C. Alliod ◽  
M. Ballivet ◽  
J.M. Matter
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Mitotic Cycle ◽  
Ventricular Zone ◽  
Helix Loop Helix ◽  
E Box ◽  
Genes Encoding ◽  
Developing Nervous System

Genes encoding transcription factors of the helix-loop-helix family are essential for the development of the nervous system in Drosophila and vertebrates. Screens of an embryonic chick neural cDNA library have yielded NeuroM, a novel neural-specific helix-loop-helix transcription factor related to the Drosophila proneural gene atonal. The NeuroM protein most closely resembles the vertebrate NeuroD and Nex1/MATH2 factors, and is capable of transactivating an E-box promoter in vivo. In situ hybridization studies have been conducted, in conjunction with pulse-labeling of S-phase nuclei, to compare NeuroM to NeuroD expression in the developing nervous system. In spinal cord and optic tectum, NeuroM expression precedes that of NeuroD. It is transient and restricted to cells lining the ventricular zone that have ceased proliferating but have not yet begun to migrate into the outer layers. In retina, NeuroM is also transiently expressed in cells as they withdraw from the mitotic cycle, but persists in horizontal and bipolar neurons until full differentiation, assuming an expression pattern exactly complementary to NeuroD. In the peripheral nervous system, NeuroM expression closely follows cell proliferation, suggesting that it intervenes at a similar developmental juncture in all parts of the nervous system. We propose that availability of the NeuroM helix-loop-helix factor defines a new stage in neurogenesis, at the transition between undifferentiated, premigratory and differentiating, migratory neural precursors.

In situ hybridization analysis of TGF beta 3 RNA expression during mouse development: comparative studies with TGF beta 1 and beta 2

Development ◽  
1990 ◽  
Vol 110 (2) ◽  
pp. 609-620 ◽  
Author(s):  
R.W. Pelton ◽  
M.E. Dickinson ◽  
H.L. Moses ◽  
B.L. Hogan
Keyword(s):  
Intervertebral Discs ◽  
The Other ◽  
Rna Expression ◽  
Tgf Beta ◽  
Mouse Development ◽  
Olfactory Bulbs ◽  
Embryonic Tissues ◽  
Organ Systems ◽  
Beta 2

To date, three closely-related TGF beta genes have been found in the mouse; TGF beta 1, TGF beta 2 and TGF beta 3. Previous experiments have indicated that TGF beta 1 and TGF beta 2 may play important roles during mouse embryogenesis. The present study now reports the distribution of transcripts of TGF beta 3 in comparison to the other two genes and reveals overlapping but distinct patterns of RNA expression. TGF beta 3 RNA is expressed in a diverse array of tissues including perichondrium, bone, intervertebral discs, mesenteries, pleura, heart, lung, palate, and amnion, as well as in central nervous system (CNS) structures such as the meninges, choroid plexus and the olfactory bulbs. Furthermore, in several organ systems, TGF beta 3 transcripts are expressed during periods of active morphogenesis suggesting that the protein may be an important factor for the growth and differentiation of many embryonic tissues.

Regulated expression and growth inhibitory effects of transforming growth factor-beta isoforms in mouse mammary gland development

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 867-878 ◽  
Author(s):  
S.D. Robinson ◽  
G.B. Silberstein ◽  
A.B. Roberts ◽  
K.C. Flanders ◽  
C.W. Daniel
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Slow Release ◽  
Mouse Mammary Gland ◽  
Tgf Beta ◽  
Growth Factor Beta ◽  
Beta 2

Transforming Growth Factor-beta 1 (TGF-beta 1) was previously shown to inhibit reversibly the growth of mouse mammary ducts when administered in vivo by miniature slow-release plastic implants. We now report a comparative analysis of three TGF-beta isoforms with respect to gene expression and localization of protein products within the mouse mammary gland. Our studies revealed overlapping expression patterns of TGF-beta 1, TGF-beta 2 and TGF-beta 3 within the epithelium of the actively-growing mammary end buds during branching morphogenesis, as well as within the epithelium of growth-quiescent ducts. However, TGF-beta 3 was the only isoform detected in myoepithelial progenitor cells (cap cells) of the growing end buds and myoepithelial cells of the mature ducts. During pregnancy, TGF-beta 2 and TGF-beta 3 transcripts increased to high levels, in contrast to TGF-beta 1 transcripts which were moderately abundant; TGF-beta 2 was significantly transcribed only during pregnancy. Molecular hybridization in situ revealed overlapping patterns of expression for the three TGF-beta isoforms during alveolar morphogenesis, but showed that, in contrast to the patterns of TGF-beta 1 and TGF-beta 2 expression, TGF-beta 3 is expressed more heavily in ducts than in alveoli during pregnancy. Developing alveolar tissue and its associated ducts displayed striking TGF-beta 3 immunoreactivity which was greatly reduced during lactation. All three isoforms showed dramatically reduced expression in lactating tissue. The biological effects of active, exogenous TGF-beta 2 and TGF-beta 3 were tested with slow-release plastic implants. These isoforms, like TGF-beta 1, inhibited mammary ductal elongation in situ by causing the disappearance of the proliferating stem cell layer (cap cells) and rapid involution of ductal end buds. None of the isoforms were active in inhibiting alveolar morphogenesis. We conclude that under the limited conditions of these tests, the three mammalian isoforms are functionally equivalent. However, striking differences in patterns of gene expression and in the distribution of immunoreactive peptides suggest that TGF-beta isoforms may have distinct roles in mammary growth regulation, morphogenesis and functional differentiation.

174 EPIDERMAL GROWTH FACTORS AND CALBINDIN-D9k GENE EXPRESSIONS DURING PREGANCY IN THE PORCINE UTERUS

2008 ◽  
Vol 20 (1) ◽  
pp. 167
Author(s):  
Y.-J. Kim ◽  
E.-M. Jung ◽  
G.-S. Lee ◽  
S.-H. Hyun ◽  
E.-B. Jeung
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Negative Control ◽  
Heparin Binding ◽  
Gene Expressions ◽  
Calbindin D9k ◽  
Genes Encoding ◽  
Epidermal Growth

To stably maintain pregnancy, several genes are expressed in the uterus. In particular, the endometrial expression of genes encoding growth factors appears to play a key role in maternal–fetal communication. Previous studies have characterized the endometrial expression kinetics of the genes encoding epidermal growth factor (EGF), its receptor (EGFR), transforming growth factor-alpha (TGF-α), amphiregulin (Areg), heparin-binding (Hb) EGF, and calbindin-D9k (CaBP-9k) in the pig during implantation. Here, we further characterized the expression patterns of these molecules during the entire porcine pregnancy. Porcine (n = 3 per PD) were collected at pregnancy days (PD) 12, 15, 30, 60, 90, and 110 and subjected to semi-quantitative RT-PCR. The data were analyzed with a nonparametric one-way analysis of variance using the Kruskal-Wallis test, followed by Dunnett's test for multiple comparisons to the negative control. EGF and EGFR showed similar expression patterns, being highly expressed around implantation time and then disappearing. TGF-α and Areg expression levels rose steadily until they peaked at PD30, after which they gradually decreased to PD12 levels. The Areg mRNA expression pattern was confirmed by real-time PCR, and similar Areg protein expression patterns were observed. Immunohistochemical analysis of PD60 uteri revealed Areg in the glandular and luminal epithelial cells. Hb-EGF was steadily expressed throughout the entire pregnancy while CaBP-9k was expressed strongly on PD12, and then declined sharply in PD15 before recovering slightly for the remainder of the pregnancy. Thus, the EGF family may play a key role during implantation in pigs. In addition, CaBP-9k may help maintain uterine quiescence during pregnancy by sequestering cytoplasmic Ca2+.

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