The surface ectoderm is essential for nephric duct formation in intermediate mesoderm

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1103-1108 ◽  
Author(s):  
T. Obara-Ishihara ◽  
J. Kuhlman ◽  
L. Niswander ◽  
D. Herzlinger

The nephric duct is the first epithelial tubule to differentiate from intermediate mesoderm that is essential for all further urogenital development. In this study we identify the domain of intermediate mesoderm that gives rise to the nephric duct and demonstrate that the surface ectoderm is required for its differentiation. Removal of the surface ectoderm resulted in decreased levels of Sim-1 and Pax-2 mRNA expression in mesenchymal nephric duct progenitors, and caused inhibition of nephric duct formation and subsequent kidney development. The surface ectoderm expresses BMP-4 and we show that it is required for the maintenance of high-level BMP-4 expression in lateral plate mesoderm. Addition of a BMP-4-coated bead to embryos lacking the surface ectoderm restored normal levels of Sim-1 and Pax-2 mRNA expression in nephric duct progenitors, nephric duct formation and the initiation of nephrogenesis. Thus, BMP-4 signaling can substitute for the surface ectoderm in supporting nephric duct morphogenesis. Collectively, these data suggest that inductive interactions between the surface ectoderm, lateral mesoderm and intermediate mesoderm are essential for nephric duct formation and the initiation of urogenital development.

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Rita Carmona ◽  
Ana Cañete ◽  
Elena Cano ◽  
Laura Ariza ◽  
Anabel Rojas ◽  
...  

Congenital diaphragmatic hernia (CDH) is a severe birth defect. Wt1-null mouse embryos develop CDH but the mechanisms regulated by WT1 are unknown. We have generated a murine model with conditional deletion of WT1 in the lateral plate mesoderm, using the G2 enhancer of the Gata4 gene as a driver. 80% of G2-Gata4Cre;Wt1fl/fl embryos developed typical Bochdalek-type CDH. We show that the posthepatic mesenchymal plate coelomic epithelium gives rise to a mesenchyme that populates the pleuroperitoneal folds isolating the pleural cavities before the migration of the somitic myoblasts. This process fails when Wt1 is deleted from this area. Mutant embryos show Raldh2 downregulation in the lateral mesoderm, but not in the intermediate mesoderm. The mutant phenotype was partially rescued by retinoic acid treatment of the pregnant females. Replacement of intermediate by lateral mesoderm recapitulates the evolutionary origin of the diaphragm in mammals. CDH might thus be viewed as an evolutionary atavism.


Development ◽  
1997 ◽  
Vol 124 (10) ◽  
pp. 1975-1984 ◽  
Author(s):  
A. Tonegawa ◽  
N. Funayama ◽  
N. Ueno ◽  
Y. Takahashi

Molecular mechanisms by which the mesoderm is subdivided along the mediolateral axis in early chicken embryos have been studied. When the presomitic mesoderm (medial mesoderm) was transplanted into the lateral plate, the graft was transformed into lateral plate tissue, indicating that the primitive somite was not fully committed and that the lateral plate has a cue for mesodermal lateralization. Since the lateral plate expresses a high level of BMP-4 mRNA, a member of the TGF-beta family, we hypothesized that it is the molecule responsible for the lateralization of the somite. To test this, we transplanted COS cells producing BMP-4 into the presomitic region. Those cells locally prevented the presomitic cells from differentiating into somites, converting them instead into lateral plate mesoderm, which was revealed by expression of cytokeratin mRNA, a marker for the lateral plate. The effect was dependent on the level of effective BMP-4: with a high level of BMP-4, the somite was transformed completely to lateral plate; with a low level, the somite formed but was occupied by the lateral somitic component expressing cSim 1, a marker for the lateral somite. These results suggest that different thresholds of effective BMP-4 determine distinct subtypes of the mesoderm as a lateralizer during early development.


Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4057-4065 ◽  
Author(s):  
M. Torres ◽  
E. Gomez-Pardo ◽  
G.R. Dressler ◽  
P. Gruss

Urogenital system development in mammals requires the coordinated differentiation of two distinct tissues, the ductal epithelium and the nephrogenic mesenchyme, both derived from the intermediate mesoderm of the early embryo. The former give rise to the genital tracts, ureters and kidney collecting duct system, whereas mesenchymal components undergo epithelial transformation to form nephrons in both the mesonephric (embryonic) and metanephric (definitive) kidney. Pax-2 is a transcriptional regulator of the paired-box family and is widely expressed during the development of both ductal and mesenchymal components of the urogenital system. We report here that Pax-2 homozygous mutant newborn mice lack kidneys, ureters and genital tracts. We attribute these defects to dysgenesis of both ductal and mesenchymal components of the developing urogenital system. The Wolffian and Mullerian ducts, precursors of male and female genital tracts, respectively, develop only partially and degenerate during embryogenesis. The ureters, inducers of the metanephros are absent and therefore kidney development does not take place. Mesenchyme of the nephrogenic cord fails to undergo epithelial transformation and is not able to form tubules in the mesonephros. In addition, we show that the expression of specific markers for each of these components is de-regulated in Pax-2 mutants. These data show that Pax-2 is required for multiple steps during the differentiation of intermediate mesoderm. In addition, Pax-2 mouse mutants provide an animal model for human hereditary kidney diseases.


2018 ◽  
Vol 10 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Charles Yoon ◽  
Hannah Song ◽  
Ting Yin ◽  
Damaris Bausch-Fluck ◽  
Andreas P. Frei ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e42228 ◽  
Author(s):  
Diana Eng ◽  
Hsiao-Yen Ma ◽  
Jun Xu ◽  
Hung-Ping Shih ◽  
Michael K. Gross ◽  
...  

Development ◽  
1990 ◽  
Vol 110 (4) ◽  
pp. 1159-1168 ◽  
Author(s):  
R. Vogels ◽  
W. de Graaff ◽  
J. Deschamps

This study reports the expression pattern of the murine homeobox-containing gene Hox-2.3 during development. Using in situ hybridization, we first detect Hox-2.3 transcripts in the allantois primordium at 7.5 days post coitum (p.c.). One day later transcripts are found in embryonic ectoderm and mesoderm. In 9.5- and 10.5- day embryos Hox-2.3 expression is observed in the central nervous system (CNS) from a rostral boundary in the upper spinal cord to the caudal end. Within this anteroposterior domain, Hox-2.3 expression is also found in the peripheral nervous system, in the mesoderm and in the hindgut epithelium. The rostral boundary in the mesoderm is located at the level of the 11th somite and thus shifted posteriorwards compared to the rostral boundary in the neural tube. During subsequent development, the initially broad expression pattern in the somitic, lateral plate and intermediate mesoderm becomes restricted to structures in the urogenital system. In adults, the spinal cord and the derivatives of the Wolffian and Mullerian ducts continue to express the gene at a high level. The described temporal and tissue-specific changes in expression of Hox-2.3 are suggestive of several levels of regulation as reported for Drosophila homeotic genes and argue for more than one role of the gene during development and in adults.


Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 151-159 ◽  
Author(s):  
J.E. Lee ◽  
J. Pintar ◽  
A. Efstratiadis

The mouse insulin-like growth factor II (IGF-II) gene encodes a polypeptide that plays a role in embryonic growth. We have examined the temporal and spatial pattern of expression of this gene in sections of the mouse conceptus between embryonic days 4.0 and 8.5 by in situ hybridization. Abundant IGF-II transcripts were detected in all the trophectodermal derivatives, after implantation. Labeling was then observed in primitive endoderm, but was transient and disappeared after formation of the yolk sac. Expression was next detected in extraembryonic mesoderm at the early primitive streak stage. Labeling in the embryo proper appeared first at the late primitive streak/neural plate stage in lateral mesoderm and in anterior-proximal cells located between the visceral endoderm and the most cranial region of the embryonic ectoderm. The position of the latter cells suggests that their descendants are likely to participate in the formation of the heart and the epithelium of the ventral and lateral walls of the foregut, where intense labeling was observed at the neural fold stage. Hybridization was also detected in cranial mesenchyme, including neural crest cells. The intensity of hybridization signal increased progressively in paraxial (presomitic and somitic) mesoderm, while declining in the ectoplacental cone. The neuroectoderm and surface ectoderm did not exhibit hybridization at any stage. Immunohistochemical analysis indicated co-localization of IGF-II transcripts, translated pre-pro-IGF-II, and the cognate IGF-II/mannose-6-phosphate receptor. These correlations are consistent with the hypothesis that IGF-II has an autocrine function.


Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Vikash Kumar ◽  
Chun Yang ◽  
Aron M Geurts ◽  
Mingyu Liang ◽  
Allen W Cowley

Pappa2 is a metalloproteinase which specifically cleaves IGFBP-3 and IGFBP-5 and in turn releases IGF-1. Recently, we have shown that a subcongenic Dahl salt-sensitive (SS) rat strain containing a 0.71 Mbp of chromosome 13 which includes Pappa2 gene from salt-insensitive Brown Norway (26-P strain) is protected significantly (24 mmHg) from salt-induced hypertension (Cowley et al., 2016). Although it is recognized that Pappa2 modulates development of bone size, cranial cartilage and angiogenesis, its role in kidney development and function is unknown. The present study determined the contribution of Pappa2 to nephron development by comparing SS and 26-P rat strains. It was found that Pappa2 mRNA expression was 5-fold higher in embryonic kidney (day 20.5) of the salt-resistant 26-P rats compared with age-matched SS rats. Pappa2 mRNA expression significantly increased with age of kidney reaching a maximum at postnatal day 5 in both strains. Pappa2 mRNA expression at postnatal day 15 was found to be 9-fold higher in the kidney of 26-P compared with SS strain. Immunohistochemistry studies revealed that Pappa2 co-localized with IGFBP-5 in the ureteric bud indicating that Pappa2 could be important for ureteric branching and nephron endowment. Glomerulus/mm 2 was therefore determined by counting total number of glomeruli in kidney sections from pups starting from P0 to P20. The salt-resistant 26-P congenic strain exhibited significantly greater nephron density 9.03 and 7.07 glo/mm 2 compared to 6.89 and 4.85 glo/mm 2 in SS rat at day P15 and P20, respectively. It appears that the Brown Norway pappa2 allele variant prevents the reduced nephron numbers observed in SS rats and thereby protects these congenic rats from salt-induced hypertension.


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