A Novel Function of DELTA-NOTCH Signalling Mediates the Transition from Proliferation to Neurogenesis in Neural Progenitor Cells

A complete account of the whole developmental process of neurogenesis involves understanding a number of complex underlying molecular processes. Among them, those that govern the crucial transition from proliferative (self-replicating) to neurogenic neural progenitor (NP) cells remain largely unknown. Due to its sequential rostro-caudal gradients of proliferation and neurogenesis, the prospective spinal cord of the chick embryo is a good experimental system to study this issue. We report that the NOTCH ligand DELTA-1 is expressed in scattered cycling NP cells in the prospective chick spinal cord preceding the onset of neurogenesis. These Delta-1-expressing progenitors are placed in between the proliferating caudal neural plate (stem zone) and the rostral neurogenic zone (NZ) where neurons are born. Thus, these Delta-1-expressing progenitors define a proliferation to neurogenesis transition zone (PNTZ). Gain and loss of function experiments carried by electroporation demonstrate that the expression of Delta-1 in individual progenitors of the PNTZ is necessary and sufficient to induce neuronal generation. The activation of NOTCH signalling by DELTA-1 in the adjacent progenitors inhibits neurogenesis and is required to maintain proliferation. However, rather than inducing cell cycle exit and neuronal differentiation by a typical lateral inhibition mechanism as in the NZ, DELTA-1/NOTCH signalling functions in a distinct manner in the PNTZ. Thus, the inhibition of NOTCH signalling arrests proliferation but it is not sufficient to elicit neuronal differentiation. Moreover, after the expression of Delta-1 PNTZ NP continue cycling and induce the expression of Tis21, a gene that is upregulated in neurogenic progenitors, before generating neurons. Together, these experiments unravel a novel function of DELTA–NOTCH signalling that regulates the transition from proliferation to neurogenesis in NP cells. We hypothesize that this novel function is evolutionary conserved

The multi-peak adaptive landscape of crocodylomorph body size evolution

Background: Little is known about the long-term patterns of body size evolution in Crocodylomorpha, the > 200-million-year-old group that includes living crocodylians and their extinct relatives. Extant crocodylians are mostly large-bodied (3–7 m) predators. However, extinct crocodylomorphs exhibit a wider range of phenotypes, and many of the earliest taxa were much smaller ( Results: Crocodylomorphs reached an early peak in body size disparity during the Late Jurassic, and underwent an essentially continual decline since then. A multi-peak Ornstein-Uhlenbeck model outperforms all other evolutionary models fitted to our data (including both uniform and non-uniform), indicating that the macroevolutionary dynamics of crocodylomorph body size are better described within the concept of an adaptive landscape, with most body size variation emerging after shifts to new macroevolutionary regimes (analogous to adaptive zones). We did not find support for a consistent evolutionary trend towards larger sizes among lineages (i.e., Cope’s rule), or strong correlations of body size with climate. Instead, the intermediate to large body sizes of some crocodylomorphs are better explained by group-specific adaptations. In particular, the evolution of a more aquatic lifestyle (especially marine) correlates with increases in average body size, though not without exceptions. Conclusions: Shifts between macroevolutionary regimes provide a better explanation of crocodylomorph body size evolution on large phylogenetic and temporal scales, suggesting a central role for lineage-specific adaptations rather than climatic forcing. Shifts leading to larger body sizes occurred in most aquatic and semi-aquatic groups. This, combined with extinctions of groups occupying smaller body size regimes (particularly during the Late Cretaceous and Cenozoic), gave rise to the upward-shifted body size distribution of extant crocodylomorphs compared to their smaller-bodied terrestrial ancestors.</p

A Regulatory Network for Coordinated Flower Maturation

For self-pollinating plants to reproduce, male and female organ development must be coordinated as flowers mature. The Arabidopsis transcription factors AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8 regulate this complex process by promoting petal expansion, stamen filament elongation, anther dehiscence, and gynoecium maturation, thereby ensuring that pollen released from the anthers is deposited on the stigma of a receptive gynoecium. ARF6 and ARF8 induce jasmonate production, which in turn triggers expression of MYB21 and MYB24, encoding R2R3 MYB transcription factors that promote petal and stamen growth. To understand the dynamics of this flower maturation regulatory network, we have characterized morphological, chemical, and global gene expression phenotypes of arf, myb, and jasmonate pathway mutant flowers. We found that MYB21 and MYB24 promoted not only petal and stamen development but also gynoecium growth. As well as regulating reproductive competence, both the ARF and MYB factors promoted nectary development or function and volatile sesquiterpene production, which may attract insect pollinators and/or repel pathogens. Mutants lacking jasmonate synthesis or response had decreased MYB21 expression and stamen and petal growth at the stage when flowers normally open, but had increased MYB21 expression in petals of older flowers, resulting in renewed and persistent petal expansion at later stages. Both auxin response and jasmonate synthesis promoted positive feedbacks that may ensure rapid petal and stamen growth as flowers open. MYB21 also fed back negatively on expression of jasmonate biosynthesis pathway genes to decrease flower jasmonate level, which correlated with termination of growth after flowers have opened. These dynamic feedbacks may promote timely, coordinated, and transient growth of flower organs

Circadian regulation of hormone signaling and plant physiology

The survival and reproduction of plants depend on their ability to cope with a wide range of daily and seasonal environmental fluctuations during their life cycle. Phytohormones are plant growth regulators that are involved in almost every aspect of growth and development as well as plant adaptation to myriad abiotic and biotic conditions. The circadian clock, an endogenous and cell-autonomous biological timekeeper that produces rhythmic outputs with close to 24-h rhythms, provides an adaptive advantage by synchronizing plant physiological and metabolic processes to the external environment. The circadian clock regulates phytohormone biosynthesis and signaling pathways to generate daily rhythms in hormone activity that fine-tune a range of plant processes, enhancing adaptation to local conditions. This review explores our current understanding of the interplay between the circadian clock and hormone signaling pathways

Lumbosacral hemivertebrae resection by combined approach - Medium- and long-term follow-up

Study Design. Retrospective review of patients records with clinical and radiographic assessment. Objectives. To evaluate the long-term result of lumbosacral hemivertebrae resection using a combined approach. Summary of Background Data. Lumbosacral hemivertebrae resection by a combined posterior and anterior approach have been previously described, but only one study is concerning such a large series of hemivertebrae. Methods. From 1980 to 2001, a consecutive series of 17 congenital scolioses due to lumbosacral hemivertebrae were managed by hemivertebrae resection using a combined approach and short anterior and posterior convex fusion. Results. The mean age at surgery was 4.9 years. The mean follow-up period was 7.6 years. One postoperative complication was encountered: a patient had motor deficit and recovery was incomplete. The mean segmental scoliosis curve was 27.5 before surgery, 10.7 after surgery, and 8.9 at the latest follow-up assessment. This represents a mean improvement of 61.1% after surgery and of 67.6% at the latest follow-up. The total main scoliosis curve improved from 28.4 degrees to 12.7 degrees and 11.4 degrees, respectively. It represents a mean improvement of 55.3% and 59.9%, respectively. The mean final lordosis was within normal values. Conclusions. This procedure offers a persistent correction with a short-segment fusion. The early surgery is able to avert severe local deformities and prevent secondary structural deformities in order to avoid extensive fusions

Sténoses post-traumatiques du grêle chez l’enfant : à propos de 2 cas

Post-traumatic small-bowel obstructions are rare and late complications following blunt abdominal trauma. Timely diagnosis is frequently impeded because of nonspecific associated symptoms, and furthermore, the degree of urgency is frequently underestimated due to the accidental cause. During the last 6 years (2005–2011), we have observed only 2 cases (4 and 10 years old) with post-traumatic small-bowel obstruction. On admission the patients had a contusion on the abdominal wall, duodenal hematoma and a Chance fracture of the lumbar spine on the computed tomography (CT) scan. Although early clinical improvement was noted, progression of the disorder was observed for the following 15 days like an occlusive syndrome (abdominal distension, nausea, emesis). Abdominal ultrasound and computed tomography scan revealed small-bowel obstruction. At laparotomy, jejunal stenosis was found associated with mesenteric tears, which was resected with end-to-end anastomosis. Six to 8 months of follow-up ascertained the therapeutic efficacy of the procedure. Post-traumatic small-bowel obstructions are rare; the clinical presentation is unspecific and appears with a time lag following the trauma. Echography and computed tomography scan can establish both the diagnosis and therapeutic choice.IIntroductionLes sténoses post-traumatiques du grêle sont une des complications tardives et rares des traumatismes fermés de l’abdomen. Leur diagnostic est difficile et peut être retardé compte tenu de leur faible fréquence et de leur mode de révélation peu spécifique.ObservationsNous rapportons 2 observations de garçons de 4 et 10 ans admis pour un traumatisme abdominal fermé à haute énergie entre 2005 et 2011. À leur admission, ils présentaient une contusion pariétale péri-ombilicale, des hématomes profonds (duodénal, caecal) et, pour l’un, une lésion type Chance en L2-3 à la tomodensitométrie (TDM). Malgré une amélioration clinique initiale, il persistait un état subocclusif (nausées et vomissements lors de la réalimentation) au-delà du 15e j. L’échographie et la TDM permettaient d’objectiver une occlusion grêlique. L’exploration chirurgicale mettait en évidence dans les 2 cas, plusieurs sténoses jéjunales associées à une dilacération du mésentère, imposant à chaque fois une résection-anastomose termino-terminale.CommentairesLes sténoses post-traumatiques du grêle sont rares et leur symptomatologie non spécifique apparaît avec un délai variable par rapport au traumatisme abdominal. La surveillance clinique, ainsi que l’échographie et la TDM permettent d’évoquer le diagnostic et de conduire à un traitement chirurgical efficace

Traumatic diaphyseal bone defects in children.

AbstractTraumatic bone defects (BD) are rare in children. There are no pediatric series in the literature on this topic. The aim of this first pediatric series was to determine the epidemiological characteristics and evaluate the results of different treatments in this entity.MATERIAL AND METHODS:This retrospective multicenter study evaluated diaphyseal bone defects in cases in which bone reconstruction was performed. BD was either initial and associated with trauma or secondary, resulting from infected non-union.RESULTS:The series included 27 patients (17 boys and 10 girls), mean age 11.4 years old (3-16) (20 traffic accidents). At the outset of all patients' history was an open fracture (one stage 1, seven stage 2, 11 stage 3A and seven stage 3B, 1 NR). BD involved 13 tibias, 9 femurs, three humerus, one radius and one ulna. Bone defects were initial in 20 cases and secondary in seven cases. They were less than 2 cm in two cases, between 2 and 5 cm in 9 cases, between 5 and 10 cm in 10 cases and more than 10 cm in six cases. Treatment of BD was immediate in one case and delayed in 26 cases. Techniques used included: induced membrane in 10 cases, bone transport in seven cases, bone autograft in eight cases, vascularized fibular transfer in one case, no bone reconstruction in one case. Union was obtained in 27 patients. Union was obtained within a mean 12.3 months BD (3-62). Fifteen patients presented with sequellae.DISCUSSION:Traumatic bone defects have a better prognosis in children than in adults. The thicker, more active and richly vascularized periosteum in children is an important prognostic factor. Treatment of BD requires good initial bone stabilization. Reconstruction depends on the integrity of the periosteum. In case of an intact periosteum, bone reconstruction does not seem necessary in young children. If one part of the periosteum is intact, a simple autograft seems sufficient even with extensive bone defects. In the absence of the periosteum or especially in case of infection, the induced membrane technique seems preferable, with bone transport or a vascularized bone transfer