Cell shape anisotropy contributes to self-organized feather pattern fidelity in birds.

Developing tissues can self-organize into a variety of patterned structures through the stabilization of stochastic fluctuations in their molecular and cellular properties. While molecular factors and cell dynamics contributing to self-organization have been identified in vivo, events channeling self-organized systems such that they achieve stable pattern outcomes remain unknown. Here, we described natural variation in the fidelity of self-organized arrays formed by feather follicle precursors in bird embryos. By surveying skin cells prior to and during tissue self-organization and performing species-specific ex vivo drug treatments and mechanical stress tests, we demonstrated that pattern fidelity depends on the initial amplitude of cell anisotropy in regions of the developing dermis competent to produce a pattern. Using live imaging, we showed that cell shape anisotropy is associated with a limited increase in cell motility for sharp and precisely located primordia formation, and thus, proper pattern geometry. These results evidence a mechanism through which initial tissue properties ensure stability in self-organization and thus, reproducible pattern production.

A conserved molecular template underlies color pattern diversity in estrildid finches.

The color patterns that adorn animals' coats not only exhibit extensive diversity linked to various ecological functions but also display recurrences in geometry, orientation, or body location. How processes of pattern formation shape such phenotypic trends remains a mystery. Here, we surveyed plumage color patterns in passerine finches displaying extreme apparent variation and identified a conserved set of color domains. We linked these domains to putative embryonic skin regions instructed by early developmental tissues and outlined by the combinatory expression of few genetic markers. We found that this embryonic prepattern is largely conserved in birds displaying drastic color differences in the adult, interspecies variation resulting from the masking or display of each domain depending on their coloration. This work showed that a simple molecular landscape serves as common spatial template to extensive color pattern variation in finches, revealing that early conserved landmarks and molecular pathways are a major cause of phenotypic trends.

Symmetry breaking in the embryonic skin triggers directional and sequential plumage patterning.

The development of an organism involves the formation of patterns from initially homogeneous surfaces in a reproducible manner. Simulations of various theoretical models recapitulate final states of natural patterns, yet drawing testable hypotheses from those often remains difficult. Consequently, little is known about pattern-forming events. Here, we surveyed plumage patterns and their emergence in Galliformes, ratites, passerines, and penguins, together representing the three major taxa of the avian phylogeny, and built a unified model that not only reproduces final patterns but also intrinsically generates shared and varying directionality, sequence, and duration of patterning. We used in vivo and ex vivo experiments to test its parameter-based predictions. We showed that directional and sequential pattern progression depends on a species-specific prepattern: an initial break in surface symmetry launches a travelling front of sharply defined, oriented domains with self-organising capacity. This front propagates through the timely transfer of increased cell density mediated by cell proliferation, which controls overall patterning duration. These results show that universal mechanisms combining prepatterning and self-organisation govern the timely emergence of the plumage pattern in birds.

Müller glial cell reactivation in Xenopus models of retinal degeneration.

A striking aspect of tissue regeneration is its uneven distribution among different animal classes, both in terms of modalities and efficiency. The retina does not escape the rule, exhibiting extraordinary self-repair properties in anamniote species but extremely limited ones in mammals. Among cellular sources prone to contribute to retinal regeneration are Müller glial cells, which in teleosts have been known for a decade to re-acquire a stem/progenitor state and regenerate retinal neurons following injury. As their regenerative potential was hitherto unexplored in amphibians, we tackled this issue using two Xenopus retinal injury paradigms we implemented: a mechanical needle poke injury and a transgenic model allowing for conditional photoreceptor cell ablation. These models revealed that Müller cells are indeed able to proliferate and replace lost cells following damage/degeneration in the retina. Interestingly, the extent of cell cycle re-entry appears dependent on the age of the animal, with a refractory period in early tadpole stages. Our findings pave the way for future studies aimed at identifying the molecular cues that either sustain or constrain the recruitment of Müller glia, an issue of utmost importance to set up therapeutic strategies for eye regenerative medicine.

Regulation of myogenesis by environmental hypoxia.

In aerobic organisms, oxygen is a critical factor for tissue and organ morphogenesis from embryonic development throughout the adult life. It regulates various intracellular pathways involved in cellular metabolism, proliferation, cell survival and fate. Organisms or tissues rapidly respond to changes in oxygen availability by activating complex signalling networks, which culminate in the control of mRNA translation and/or gene expression. This Commentary presents the effects of hypoxia during embryonic development, myoblasts and satellite cell proliferation and differentiation in vertebrates. We also outline the relationship between Notch, Wnt and growth factor signalling pathways, as well as the post-transcriptional regulation of myogenesis under conditions of hypoxia.

The dystroglycan: nestled in an adhesome during embryonic development.

Invertebrate and vertebrate development relies on complex processes that require many coordinated cell functions including cell adhesion, migration, proliferation and polarization. These processes depend on tissues and are spatio-temporally regulated by specific interactions between cells and between cells and the extracellular matrices. The dystroglycan, a transmembrane receptor that binds multiple extracellular matrix proteins, is expressed from oogenesis to organogenesis. There are increasing data suggesting that the axis, consisting of extracellular component-dystroglycan-cytoplasmic proteins, controls both the adhesion of cells to matrices as well as the transduction of signals coming from or directed to matrices. In this article, we review current advances leading to consider that the dystroglycan is a key protein nestled in an adhesome involved in mechanisms of cell adhesion during embryonic development.

Oxygen modulates the glutathione peroxidase activity during the L6 myoblast early differentiation process.

AIM: This work aims to study the regulation of the glutathione peroxidase and catalase activities in myoblasts from the L6 line exposed to 21%, 5% and 1% O2 during the cell differentiation. MATERIAL AND METHODS: Rat L6 myoblasts were grown in 1%, 5% or 21% O2 in the presence or absence of N-acetyl cysteine. The cell proliferation was evaluated by determining the doubling time and kinetics of cultures by counting cells. The cell differentiation was analyzed by determining the myogenic fusion index using antibodies against the myosin heavy chain. The glutathione peroxidase and catalase activities were assayed. The p110-PI3K/Thr308-Akt pathway was studied using western blotting. The oxidative status of the cells was carried out by determining TBARS. RESULTS: 5% O2 improves the glutathione peroxidase activity, p110-PI3K/Thr308-Akt pathway and differentiation while 1% O2 alters all these parameters compared to 21% O2. NAC (0.5 mM) can prevent the deleterious effects of hypoxia (1% O2) on the L6 myoblast proliferation and enhances the myoblast differentiation when exposed to 21% O2. TBARS are reduced in 5% O2 compared to both 21% and 1% O2. CONCLUSION: The glutathione peroxidase activity and p110-PI3K/Thr308-Akt are both modulated in the same way by oxygen.

The translational repressor 4E-BP mediates hypoxia-induced defects in myotome cells.

Cell growth, proliferation, differentiation and survival are influenced by the availability of oxygen. The effect of hypoxia on embryonic cells and the underlying molecular mechanisms to maintain cellular viability are still poorly understood. In this study, we show that hypoxia during Xenopus embryogenesis rapidly leads to a significant developmental delay and to cell apoptosis after prolonged exposure. We provide strong evidence that hypoxia does not affect somitogenesis but affects the number of mitotic cells and muscle-specific protein accumulation in somites, without interfering with the expression of MyoD and MRF4 transcription factors. We also demonstrate that hypoxia reversibly decreases Akt phosphorylation and increases the total amount of the translational repressor 4E-BP, in combination with an increase of the 4E-BP associated with eIF4E. Interestingly, the inhibition of PI3-kinase or mTOR, with LY29002 or rapamycin, respectively, triggers the 4E-BP accumulation in Xenopus embryos. Finally, the overexpression of the non-phosphorylatable 4E-BP protein induces, similar to hypoxia, a decrease in mitotic cells and a decrease in muscle-specific protein accumulation in somites. Taken together, our studies suggest that 4E-BP plays a central role under hypoxia in promoting the cap-independent translation at the expense of cap-dependent translation and triggers specific defects in muscle development.

Dystroglycan is involved in skin morphogenesis downstream of the Notch signaling pathway.

Dystroglycan (Dg) is a transmembrane protein involved both in the assembly and maintenance of basement membrane structures essential for tissue morphogenesis, and the transmission of signals across the plasma membrane. We used a morpholino knockdown approach to investigate the function of Dg during Xenopus laevis skin morphogenesis. The loss of Dg disrupts epidermal differentiation by affecting the intercalation of multiciliated cells, deposition of laminin, and organization of fibronectin in the extracellular matrix (ECM). Depletion of Dg also affects cell-cell adhesion, as shown by the reduction of E-cadherin expression at the intercellular contacts, without affecting the distribution of ß(1) integrins. This was associated with a decrease of cell proliferation, a disruption of multiciliated-cell intercalation, and the down-regulation of the transcription factor P63, a marker of differentiated epidermis. In addition, we demonstrated that inhibition or activation of the Notch pathway prevents and promotes transcription of X-dg. Our study showed for the first time in vivo that Dg, in addition to organizing laminin in the ECM, also acts as a key signaling component in the Notch pathway.

In vivo analyzes of dystroglycan function during somitogenesis in Xenopus laevis.

Dystroglycan (Dg) is a cell adhesion receptor for laminin that has been reported to play a role in skeletal muscle cell stability, cytoskeletal organization, cell polarity, and signaling. Here we show that Dg is expressed at both the notochord/somite and the intersomitic boundaries, where laminin and fibronectin are accumulated during somitogenesis. Inhibition of Dg function with morpholino antisense oligonucleotides or a dominant negative mutant results in the normal segmentation of the presomitic mesoderm but affects the number, the size, and the integrity of somites. Depletion of Dg disrupts proliferation and alignment of myoblasts without affecting XMyoD and XMRF4 expression. It also leads to defects in laminin deposition at the intersomitic junctions, whereas expression of integrin beta1 subunits and fibronectin assembly occur normally. Our results show that Dg is critical for both proliferation and elongation of somitic cells and that the Dg-cytoplasmic domain is required for the laminin assembly at the intersomitic boundaries. Developmental Dynamics 238:1332-1345, 2009. (c) 2008 Wiley-Liss, Inc.

Uso indebido de drogas en estudiantes de 6to año de medicina / Undue use of drugs in interns of Faculties of Medical Sciences in Havana City

Se hace un reporte acerca de una investigación realizada como trabajo de terminación de la residencia de una de las autoras que consistió en un estudio observacional de corte transversal, empleando la técnica del muestreo probabilístico; mediante la aplicación de una encuesta dirigida a 108 estudiantes de sexto año de la Carrera de Medicina de cinco de las Facultades de Ciencias Medicas de Ciudad de La Habana, durante el examen estatal del curso 1999-2000, con el objetivo de indagar acerca del consumo de sustancias psicotropas. El estudio reveló que las sustancias más consumidas fueron las drogas lícitas; dentro de ellas el alcohol, los psicofármacos y el cigarro. El consumo de drogas ilícitas representó 1(por ciento)del total, porcentaje suficiente para que se adopten medidas encaminadas a la prevención en este importante sector para la Salud Pública, por lo que se hacen recomendaciones al respecto

Uso indebido de drogas en estudiantes de 6to año de medicina / Undue use of drugs in interns of Faculties of Medical Sciences in Havana City

Se hace un reporte acerca de una investigación realizada como trabajo de terminación de la residencia de una de las autoras que consistió en un estudio observacional de corte transversal, empleando la técnica del muestreo probabilístico; mediante la aplicación de una encuesta dirigida a 108 estudiantes de sexto año de la Carrera de Medicina de cinco de las Facultades de Ciencias Medicas de Ciudad de La Habana, durante el examen estatal del curso 1999-2000, con el objetivo de indagar acerca del consumo de sustancias psicotropas. El estudio reveló que las sustancias más consumidas fueron las drogas lícitas; dentro de ellas el alcohol, los psicofármacos y el cigarro. El consumo de drogas ilícitas representó 1(por ciento)del total, porcentaje suficiente para que se adopten medidas encaminadas a la prevención en este importante sector para la Salud Pública, por lo que se hacen recomendaciones al respecto(AU)