Genetically programmed retinoic acid deficiency during gastrulation phenocopies most known developmental defects due to acute prenatal alcohol exposure in FASD

Fetal Alcohol Spectrum Disorder (FASD) arises from maternal consumption of alcohol during pregnancy affecting 2%–5% of the Western population. In Xenopus laevis studies, we showed that alcohol exposure during early gastrulation reduces retinoic acid (RA) levels at this critical embryonic stage inducing craniofacial malformations associated with Fetal Alcohol Syndrome. A genetic mouse model that induces a transient RA deficiency in the node during gastrulation is described. These mice recapitulate the phenotypes characteristic of prenatal alcohol exposure (PAE) suggesting a molecular etiology for the craniofacial malformations seen in children with FASD. Gsc+/Cyp26A1 mouse embryos have a reduced RA domain and expression in the developing frontonasal prominence region and delayed HoxA1 and HoxB1 expression at E8.5. These embryos also show aberrant neurofilament expression during cranial nerve formation at E10.5 and have significant FASD sentinel-like craniofacial phenotypes at E18.5. Gsc+/Cyp26A1 mice develop severe maxillary malocclusions in adulthood. Phenocopying the PAE-induced developmental malformations with a genetic model inducing RA deficiency during early gastrulation strongly supports the alcohol/vitamin A competition model as a major molecular etiology for the neurodevelopmental defects and craniofacial malformations seen in children with FASD

Writing Russia's future: paradigms, drivers, and scenarios

The development of prediction and forecasting in the social sciences over the past century and more is closely linked with developments in Russia. The Soviet collapse undermined confidence in predictive capabilities, and scenario planning emerged as the dominant future-oriented methodology in area studies, including the study of Russia. Scenarists anticipate multiple futures rather than predicting one. The approach is too rarely critiqued. Building on an account of Russia-related forecasting in the twentieth century, analysis of two decades of scenarios reveals uniform accounts which downplay the insights of experts and of social science theory alike

The opposing homeobox genes Goosecoid and Vent1/2 self-regulate Xenopus patterning

We present a loss-of-function study using antisense morpholino (MO) reagents for the organizer-specific gene Goosecoid (Gsc) and the ventral genes Vent1 and Vent2. Unlike in the mouse Gsc is required in Xenopus for mesodermal patterning during gastrulation, causing phenotypes ranging from reduction of head structures—including cyclopia and holoprosencephaly—to expansion of ventral tissues in MO-injected embryos. The overexpression effects of Gsc mRNA require the expression of the BMP antagonist Chordin, a downstream target of Gsc. Combined Vent1 and Vent2 MOs strongly dorsalized the embryo. Unexpectedly, simultaneous depletion of all three genes led to a rescue of almost normal development in a variety of embryological assays. Thus, the phenotypic effects of depleting Gsc or Vent1/2 are caused by the transcriptional upregulation of their opposing counterparts. A principal function of Gsc and Vent1/2 homeobox genes might be to mediate a self-adjusting mechanism that restores the basic body plan when deviations from the norm occur, rather than generating individual cell types. The results may shed light on the molecular mechanisms of genetic redundancy

Maternal xNorrin, a Canonical Wnt Signaling Agonist and TGF-β Antagonist, Controls Early Neuroectoderm Specification in Xenopus

Xenopus maternal Norrin, which activates Wnt signaling but inhibits TGF-β family molecules, is essential for neuroectoderm formation. Loss of TGF-β inhibition in Norrin may contribute to the development of Norrie disease

Tsukushi Modulates Xnr2, FGF and BMP Signaling: Regulation of Xenopus Germ Layer Formation

Cell-cell communication is essential in tissue patterning. In early amphibian development, mesoderm is formed in the blastula-stage embryo through inductive interactions in which vegetal cells act on overlying equatorial cells. Members of the TGF-beta family such as activin B, Vg1, derrière and Xenopus nodal-related proteins (Xnrs) are candidate mesoderm inducing factors, with further activity to induce endoderm of the vegetal region. TGF-beta-like ligands, including BMP, are also responsible for patterning of germ layers. In addition, FGF signaling is essential for mesoderm formation whereas FGF signal inhibition has been implicated in endoderm induction. Clearly, several signaling pathways are coordinated to produce an appropriate developmental output; although intracellular crosstalk is known to integrate multiple pathways, relatively little is known about extracellular coordination

SNW1 Is a Critical Regulator of Spatial BMP Activity, Neural Plate Border Formation, and Neural Crest Specification in Vertebrate Embryos

In frog and fish embryos, SNW1 is a protein required for the spatio-temporal activity of BMP signaling necessary for neural plate border formation and specification of neural crest tissue

Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling Pathway

Protein Kinase Domain Containing, Cytoplasmic (PKDCC) is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP) molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway.Fundacao Ciencia e Tecnologia - IP; IBB/CBME, LA [PTDC/BIA-BCM/69912/2006, Pest-OE/EQB/LA0023/2013]; FCTinfo:eu-repo/semantics/publishedVersio