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Embryogenesis relies on the precise interplay of signaling cascades to activate tissue-specific differentiation programs. An important player in these morphogenetic processes is .-catenin, which is a central component of adherens junctions and canonical Wnt signaling. Lack of &bgr;-catenin is lethal before gastrulation, but mice heterozygous for &bgr;-catenin (Ctnnb1) develop as wild type. Here, we confine &bgr;-catenin amounts below the heterozygous expression level to study the functional consequences for development. We generate embryonic stem (ES) cells and embryos expressing &bgr;-catenin only from the ubiquitously active ROSA26 promoter and thereby limit &bgr;-catenin expression to ∼12.5% (ROSA26&bgr;/+) or ∼25% (ROSA26&bgr;/&bgr;) of wild-type levels. ROSA26&bgr;/+ is sufficient to maintain ES cell morphology and pluripotent characteristics, but is insufficient to activate canonical target genes upon Wnt stimulation. This Wnt signaling deficiency is incompletely restored in ROSA26&bgr;/&bgr; ES cells. We conclude that even very low &bgr;-catenin levels are able to sustain cell adhesion, but not Wnt signaling. During development, ROSA26&bgr;/&bgr; as well as ROSA26&bgr;/+ partially rescues the knockout phenotype, yet proper gastrulation is absent. These embryos differentiate according to the neural default hypothesis, indicating that gastrulation depends on high &bgr;-catenin levels. Strikingly, if ROSA26&bgr;/+ or ROSA26&bgr;/&bgr; is first activated after gastrulation, subsequent development correlates with the dosage of &bgr;-catenin. Moreover, molecular evidence indicates that the amount of &bgr;-catenin controls the induction of specific Wnt target genes. In conclusion, by restricting its expression we determine the level of &bgr;-catenin required for adhesion or pluripotency and during different morphogenetic events. [ABSTRACT FROM AUTHOR]

Background In pregnancy, a high plasma volume maintains uteroplacental perfusion and prevents placental ischemia, a condition linked to elevated maternal blood pressure ( BP ). Reducing BP by increasing Na + intake via plasma volume expansion appears contra-intuitive. We hypothesize that an appropriate Na + intake in pregnancy reduces maternal BP and adapts the renin-angiotensin system in a pregnancy-specific manner. Methods and Results BP was measured by implanted telemetry in Sprague-Dawley rats before and throughout pregnancy. Pregnant and nonpregnant animals received either a normal-salt (0.4%; NS ), high-salt (8%; HS ), or low-salt (0.01%; LS ) diet, or HS (days 1-14) followed by LS (days 14-20) diet ( HS / LS ). Before delivery (day 20), animals were euthanized and organs collected. Food, water, and Na + intake were monitored in metabolic cages, and urinary creatinine and Na + were analyzed. Na + intake and retention increased in pregnancy ( NS , LS ), leading to a positive Na + balance ( NS , LS ). BP was stable during LS , but reduced in HS conditions in pregnancy. The renin-angiotensin system was adapted as expected. Activating cleavage of α- and γ-subunits of the renal epithelial Na + channel and expression of-full length medullary β-subunits, accentuated further in all LS conditions, were upregulated in pregnancy. Conclusions Pregnancy led to Na + retention adapted to dietary changes. HS exposure paradoxically reduced BP . Na + uptake while only modestly linked to the renin-angiotensin system is enhanced in the presence of posttranslational renal epithelial Na + channel modifications. This suggests (1) storage of Na + in pregnancy upon HS exposure, bridging periods of LS availability; and (2) that potentially non-renin-angiotensin-related mechanisms participate in EN aC activation and consecutive Na + retention.

Vertebrates have a metameric bodyplan that is based on the presence of paired somites. Somites develop from the segmental plate in a cranio-caudal sequence. At the same time, new material is added from Hensen's node, the primitive streak and the tailbud. In this way, the material residing in the segmental plate remains constant and comprises 12 prospective somites on each side. Prospective segment borders are not yet determined in the caudal segmental plate. Prior to segmentation, the cranial segmental plate undergoes epithelialization, which is controlled by signals from the neural tube and ectoderm. The bHLH transcription factor Paraxis is critically involved in this process. Formation of a new somite from the cranial end of the segmental plate is a highly controlled process involving complex cell movements in relation to each other. Hox genes specify regional identity of the somites and their derivatives. In the chicken a transposition of thoracic into cervical vertebrae has occurred as compared to the mouse. Transcription factors of the bHLH and homeodomain type also specify the cranio-caudal polarity and that of particular cell groups within the somites. According to segmentation models, somitogenesis is under the control of a "segmentation clock" in combination with a morphogen gradient. This hypothesis has recently found support from molecular data, especially the cycling expression of genes such as cHairy1 and Lunatic Fringe, which depend on the Notch/Delta pathway of signal transduction. FGF8 has been described to be distributed along a cranio-caudal gradient. The first oscillating gene described shown to be independent of Notch is Axin2, encoding a negative regulator of the canonical Wnt pathway and a target of Wnt3a. Wnt3a and Axin2 show a similar distribution as FGF8 with high levels in the tailbud. The chick embryo has recently become accessible to molecular approaches such as overexpression by electroporation and RNA interference which can be expected to help elucidating some of the still open questions concerning somitogenesis.