Disease relevance of Germ Layers

• Tse-1 was active in nonhepatic cell lines derived from each primary germ layer, but Tse-1 activity was not apparent in hybrids between hepatoma cells and primary mouse hepatocytes [1].
• Pluripotent mouse P19 embryonal carcinoma (EC) cells have been extensively used as a developmental model system because they can differentiate in the presence of retinoic acid (RA) into derivatives of all three germ layers depending on RA dosage and culture conditions [2].
• Further characterization of the goosecoid-overexpressing ES cells revealed that they maintain the expression of stage-specific embryonic antigen-1, and teratomas derived from goosecoid-overexpressing cells show the presence of cell types derived from all three germ layers [3].

High impact information on Germ Layers

• We provide genetic and molecular evidence that the ability and sensitivity of ES cells to differentiate into the three germ layers is inhibited by increased doses of beta-catenin by specific Apc mutations [4].
• In contrast, Smad2 mutants entirely lack tissues of the embryonic germ layers [5].
• The role of maternal VegT in establishing the primary germ layers in Xenopus embryos [6].
• Differential regulation of Ultrabithorax in two germ layers of Drosophila [7].
• Sp1/egr-like zinc-finger protein required for endoderm specification and germ-layer formation in Drosophila [8].

Biological context of Germ Layers

• Strong homologies extend over the entire 6 kb of the ftz upstream region with the best match in the 'upstream element'. We identified several highly conserved boxes embedded in unrelated sequences that correspond extremely well to two germ layer specific enhancers in the upstream element [9].
• In Caenorhabditis elegans and sea urchins, canonical Notch signaling is essential for different cell fate specifications during early embryogenesis or the formation of endoderm, mesoderm, or ectoderm germ layers [10].
• Homozygotes continued to develop for 2-3 more days, reaching the size of a normal 8.5 day embryo, and formed tissues representative of all three germ layers, including several differentiated cell types [11].
• The homeobox gene goosecoid (gsc) and the winged-helix gene Hepatic Nuclear Factor-3beta (HNF-3beta) are co-expressed in all three germ layers in the anterior primitive streak and at the rostral end of mouse embryos during gastrulation [12].
• Immunohistochemical analysis demonstrates that Bcl-2 is widely expressed early in mouse fetal development in tissues derived from all three germ layers and that this expression becomes restricted with maturation [13].

Anatomical context of Germ Layers

• These studies establish that Htl signaling provides a vital connection between initial formation of the embryonic mesoderm in Drosophila and subsequent cell-fate specification within this germ layer [14].
• The coincidence of E-cadherin expression with the process of gastrulation and its restriction to the ectoderm indicate that it may play a role in the morphogenetic movements of gastrulation and resulting segregation of embryonic germ layers [15].
• Although VHL mRNA was expressed in all three germ layers, strong expression was noted in the central nervous system, kidneys, testis and lung [16].
• As the primitive streak forms, Otx2 expression is restricted to the anterior parts of all three germ layers [17].
• During development, CCN3 is expressed widely in derivatives of all three germ layers, and high levels of expression are observed in smooth muscle cells of the arterial vessel wall [18].

Associations of Germ Layers with chemical compounds

• To identify how RA signals to pancreatic progenitors in the endoderm, we have developed a novel cell transplantation technique, using the ability of the SOX32 transcription factor to confer endodermal identity, to selectively target reagents to (or exclude them from) the endodermal germ layer of the zebrafish [19].
• XLFB3 is not expressed in the rostral part of all three germ layers, with coincident anterior borders that are shifted anteriorly by treatment of developing embryos with retinoic acid [20].
• In addition, a range of morphological defects in other germ layers is seen, and cell movement is adversely affected by methanol exposure [21].
• Using histochemical methods the authors studied the effect of ACTH and cortisone on carbohydrate-protein complexes of epithelial cells derived from 3 different germ layers [22].
• Isolated explants from axolotl early gastrulae show three types of behaviour in terms of glycoprotein synthesis, corresponding to the classical germ layers [23].

Gene context of Germ Layers

• Loss of Frem2 function results in defects in developmental events associated with morphogenetic rearrangements of the vasculature and of tissues arising from all germ layers [24].
• Homozygous mutant embryos derived from eggs lacking Pofut1 gene transcripts developed indistinguishably from the wild type until approximately embryonic day 8.0, a postgastrulation stage after the formation of the three germ layers [10].
• Mesodermal expression of dpp is required for the expression of lab in these endodermal cells indicating that dpp mediates an inductive interaction between the two germ layers [25].
• The combination of an ectoderm-specific regulatory mutation in the Hoxb1 locus and the Hoxa1 mutant genetic background results in an ectoderm-specific double mutation, leaving the other germ layers impaired only in Hoxa1 function [26].
• Two of the three mouse Cdx paralogues, Cdx 1 and Cdx2, are expressed early in a Hox-like manner in the three germ layers [27].

Analytical, diagnostic and therapeutic context of Germ Layers

• Antibody staining and in situ hybridization reveal that B-cadherin protein and mRNA are found in diverse epithelia derived from each of the three primary germ layers, where their expression is strikingly regulated during differentiation [28].
• With RT-PCR, expression of the signaling TGF-beta receptors (types II and ALK-5) was shown to be absent in isolated germ layers of 6.0-7.5 days postcoitum (dpc) embryos, whereas the type III receptor and Tsk 7L were differentially expressed at these stages [29].
• Immunocytochemistry revealed the presence of PRLR in early post-hatching stages of larvae in tissues derived from all three germ layers [30].
• Mouse embryos lacking Pofut1 develop normally through blastogenesis to E8.0 when all three germ layers have formed [31].

References