Ipsographing the Dubject; or, The Contradictions of Twitter

Precise control of self-renewal and differentiation of progenitor cells into the cranial neural crest (CNC) pool ensures proper head development, guided by signaling pathways such as BMPs, FGFs, Shh and Notch. Here, we show that murine Sox2 plays an essential role in controlling progenitor cell behavior during craniofacial development. A "Conditional by Inversion" Sox2 allele (Sox2(COIN) ) has been employed to generate an epiblast ablation of Sox2 function (Sox2(EpINV) ). Sox2 (EpINV/+(H)) haploinsufficient and conditional (Sox2(EpINV/mosaic) ) mutant embryos proceed beyond gastrulation and die around E11. These mutant embryos exhibit severe anterior malformations, with hydrocephaly and frontonasal truncations, which could be attributed to the deregulation of CNC progenitor cells during their epithelial to mesenchymal transition. This irregularity results in an exacerbated and aberrant migration of Sox10(+) NCC in the branchial arches and frontonasal process of the Sox2 mutant embryos. These results suggest a novel role for Sox2 as a regulator of the epithelial to mesenchymal transitions (EMT) that are important for the cell flow in the developing head

Developmental expression of retinoic acid receptors (RARs)

Here, I review the developmental expression features of genes encoding the retinoic acid receptors (RARs) and the 'retinoid X' or rexinoid receptors (RXRs). The first detailed expression studies were performed in the mouse over two decades ago, following the cloning of the murine Rar genes. These studies revealed complex expression features at all stages of post-implantation development, one receptor gene (Rara) showing widespread expression, the two others (Rarb and Rarg) with highly regionalized and/or cell type-specific expression in both neural and non-neural tissues. Rxr genes also have either widespread (Rxra, Rxrb), or highly-restricted (Rxrg) expression patterns. Studies performed in zebrafish and Xenopus demonstrated expression of Rar and Rxr genes (both maternal and zygotic), at early pre-gastrulation stages. The eventual characterization of specific enzymes involved in the synthesis of retinoic acid (retinol/retinaldehyde dehydrogenases), or the triggering of its catabolism (CYP26 cytochrome P450s), all of them showing differential expression patterns, led to a clearer understanding of the phenomenons regulated by retinoic acid signaling during development. Functional studies involving targeted gene disruptions in the mouse, and additional approaches such as dominant negative receptor expression in other models, have pinpointed the specific, versus partly redundant, roles of the RARs and RXRs in many developing organ systems. These pleiotropic roles are summarized hereafter in relationship to the receptors’ expression patterns

Enamel and dental anomalies in latent-transforming growth factor beta-binding protein 3 mutant mice.

Latent-transforming growth factor beta-binding protein 3 (LTBP-3) is important for craniofacial morphogenesis and hard tissue mineralization, as it is essential for activation of transforming growth factor-β (TGF-β). To investigate the role of LTBP-3 in tooth formation we performed micro-computed tomography (micro-CT), histology, and scanning electron microscopy analyses of adult Ltbp3-/- mice. The Ltbp3-/- mutants presented with unique craniofacial malformations and reductions in enamel formation that began at the matrix formation stage. Organization of maturation-stage ameloblasts was severely disrupted. The lateral side of the incisor was affected most. Reduced enamel mineralization, modification of the enamel prism pattern, and enamel nodules were observed throughout the incisors, as revealed by scanning electron microscopy. Molar roots had internal irregular bulbous-like formations. The cementum thickness was reduced, and microscopic dentinal tubules showed minor nanostructural changes. Thus, LTBP-3 is required for ameloblast differentiation and for the formation of decussating enamel prisms, to prevent enamel nodule formation, and for proper root morphogenesis. Also, and consistent with the role of TGF-β signaling during mineralization, almost all craniofacial bone components were affected in Ltbp3-/- mice, especially those involving the upper jaw and snout. This mouse model demonstrates phenotypic overlap with Verloes Bourguignon syndrome, also caused by mutation of LTBP3, which is hallmarked by craniofacial anomalies and amelogenesis imperfecta phenotypes.journal article2017 Febimporte

Endogenous retinoic acid signaling is required for maintenance and regeneration of cornea

Retinoic acid (RA) is a biologically active metabolite of vitamin A (retinol) that serves as an important signaling molecule in orchestrating diverse developmental processes including multiple roles during ocular development. Loss-of-function studies using gene knockouts of RA-synthesizing enzymes encoded by Aldh1a1, Aldh1a2, and Aldh1a3 (also known as Raldh1, Raldh2, and Raldh3) have provided valuable insight into how RA controls eye morphogenesis including corneal development. However, it is unclear whether endogenous RA is required for maintenance and regeneration of adult cornea. Here, we investigated the role of Aldh1a genes in the adult cornea using a novel conditional Aldh1a1,2,3-flox/flox;Rosa26-CreERT2 loss-of-function mouse model to determine the biological function of RA. Our findings indicate that loss of RA synthesis results in corneal thinning characterized by reduced thickness of the stromal layer, impaired corneal epithelial cell proliferation, and increased apoptosis. Corneal thinning in Aldh1a-deficient mice was significantly rescued by RA administration, indicating an important role of endogenous RA signaling in adult corneal homeostasis and regeneration. Thus, Aldh1a1,2,3-flox/flox;Rosa26-CreERT2 mice provide a useful model for investigating the mechanistic role of RA signaling in adult corneal maintenance and could provide new insights into therapeutic approaches for controlling corneal repair to prevent vision loss.PMC536340

Cohesion, performance, and satisfaction in the co-acting sport of collegiate wrestling

This investigation was designed to examine the relationship between cohesion and absolute success, relative success, and satisfaction/enjoyment in the co-acting sport of collegiate wrestling. Cohesion was assessed by the Group Environment Questionnaire (GEQ) (Widmeyer, Brawley, & Carron, 1985) which measures four aspects of cohesion. Performance was measured by absolute success, relative success, and tournament placement.^ Data was gathered from the NC A Division III intercollegiate wrestling teams in the NECCWA. A total of 112 subjects completed the study. The GEQ was administered to the 12 teams early in the season, at midseason, and at the last regular season competition.^ The hypotheses of this study suggested positive correlation and prediction relationships between the individual and team scores on the four GEQ measures of cohesion, and relative success, absolute success, and satisfaction/enjoyment. The data was analyzed using Pearson product moment correlation coefficients, several multiple regression analyses, and several discriminant function analyses.^ The strongest and most consistent relationship found throughout this study was the significant positive relationship between cohesion and satisfaction/enjoyment, In the multiple regression analysis, satisfaction/enjoyment significantly predicted individual GEQ scores, while individual GEQ scores significantly predicted satisfaction/enjoyment.^ Some strong positive correlations existed between a team\u27s cohesion and a team\u27s absolute and relative success. Due to the small sample size of 12 teams and the necessary alpha level adjustment for multiple tests, these correlations were not significant. However, these results do suggest that in the co-acting sport of collegiate wrestling, there may be a positive relationship between cohesion and performance.^ Past research does not make it clear whether team cohesion in a co-acting sport should be encouraged or discouraged as a means to enhance performance and satisfaction/enjoyment. The results of this study along with Williams and Widmeyer (1991) suggest that cohesion should be encouraged in co-acting sports teams.^ Further study is recommended to examine the relationship between cohesion, performance and satisfaction/enjoyment in co-acting sports. These studies should utilize the GEQ to assess cohesion, and attempt to examine large numbers of teams and athletes.

Vax2 regulates retinoic acid distribution and cone opsin expression in the vertebrate eye

Vax2 is an eye-specific homeobox gene, the inactivation of which in mouse leads to alterations in the establishment of a proper dorsoventral eye axis during embryonic development. To dissect the molecular pathways in which Vax2 is involved, we performed a transcriptome analysis of Vax2(-/-) mice throughout the main stages of eye development. We found that some of the enzymes involved in retinoic acid (RA) metabolism in the eye show significant variations of their expression levels in mutant mice. In particular, we detected an expansion of the expression domains of the RA-catabolizing enzymes Cyp26a1 and Cyp26c1, and a downregulation of the RA-synthesizing enzyme Raldh3. These changes determine a significant expansion of the RA-free zone towards the ventral part of the eye. At postnatal stages of eye development, Vax2 inactivation led to alterations of the regional expression of the cone photoreceptor genes Opn1sw (S-Opsin) and Opn1mw (M-Opsin), which were significantly rescued after RA administration. We confirmed the above described alterations of gene expression in the Oryzias latipes (medaka fish) model system using both Vax2 gain- and loss-of-function assays. Finally, a detailed morphological and functional analysis of the adult retina in mutant mice revealed that Vax2 is necessary for intraretinal pathfinding of retinal ganglion cells in mammals. These data demonstrate for the first time that Vax2 is both necessary and sufficient for the control of intraretinal RA metabolism, which in turn contributes to the appropriate expression of cone opsins in the vertebrate eye