Analysis of mouse embryonic patterning and morphogenesis by forward genetics

Many aspects of the genetic control of mammalian embryogenesis cannot be extrapolated from other animals. Taking a forward genetic approach, we have induced recessive mutations by treatment of mice with ethylnitrosourea and have identified 43 mutations that affect early morphogenesis and patterning, including 38 genes that have not been studied previously. The molecular lesions responsible for 14 mutations were identified, including mutations in nine genes that had not been characterized previously. Some mutations affect vertebrate-specific components of conserved signaling pathways; for example, at least five mutations affect previously uncharacterized regulators of the Sonic hedgehog (Shh) pathway. Approximately half of all of the mutations affect the initial establishment of the body plan, and several of these produce phenotypes that have not been described previously. A large fraction of the genes identified affect cell migration, cellular organization, and cell structure. The findings indicate that phenotype-based genetic screens provide a direct and unbiased method to identify essential regulators of mammalian development.     

Origin of the sinoatrial node and atrioventricular node arteries in right, mixed, and left inferior emphasis systems.

The origin of the sinoatrial node artery (SAN) and atrioventricular node artery (AVN) was determined for 118 patients with normal coronary arteriograms. The coronary arteriograms of the 118 patients were divided into right (66.1%), mixed (26.3%), and left (7.6%) inferior emphasis systems. The SAN arose from the right coronary artery in 53%, the left coronary artery in 35%, and had a dual origin in 11%. The proximal right coronary artery was the origin of the SAN in 48.7% of right, 60.5% of mixed, and 55.6% of left inferior emphasis systems. The left coronary artery was the origin of the SAN in 38.5% of right, 25.8% of mixed, and 44.4% of left inferior emphasis systems. The AVN arose from the right coronary artery in 84%, the left coronary artery in 8%, and from both in 8% of the 118 patients. The right coronary artery was the origin of the AVN in 98.7% of right, 74.2% of mixed, and 0% of left inferior emphasis systems. The left coronary artery was the origin of the AVN in 0% of right, 25.8% of mixed, and 100% of left inferior emphasis systems.     

Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling

New blood vessels arise initially as blood islands in the process known as vasculogenesis or as new capillary segments produced through angiogenesis. Angiogenesis itself encompasses two broad processes, namely sprouting (SA) and intussusceptive (IA) angiogenesis. Primordial capillary plexuses expand through both SA and IA, but subsequent growth and remodeling are achieved through IA. The latter process proceeds through transluminal tissue pillar formation and subsequent vascular splitting, and the direction taken by the pillars delineates IA into overt phases, namely: intussusceptive microvascular growth, intussusceptive arborization, and intussusceptive branching remodeling. Intussusceptive microvascular growth circumscribes the process of initiation of pillar formation and their subsequent expansion with the result that the capillary surface area is greatly enhanced. In contrast, intussusceptive arborization entails formation of serried pillars that remodel the disorganized vascular meshwork into the typical tree-like arrangement. Optimization of local vascular branching geometry occurs through intussusceptive branching remodeling so that the vasculature is remodeled to meet the local demand. In addition, IA is important in creation of the local organ-specific angioarchitecture. While hemodynamic forces have proven direct effects on IA, with increase in blood flow resulting in initiation of pillars, the preponderant mechanisms are unclear. Molecular control of IA has so far not been unequivocally elucidated but interplay among several factors is probably involved. Future investigations are strongly encouraged to focus on interactions among angiogenic growth factors, angiopoetins, and related receptors.     

Changes in right ventricular filling dynamics during left anterior descending, left circumflex and right coronary artery balloon occlusion

AIM: Transient coronary artery occlusion during percutaneous transluminalcoronary angioplasty may cause left ventricular diastolic dysfunction.The aim of this study was to evaluate the effect of left anteriordescending, left circumflex and right coronary artery balloonocclusion on right ventricular diastolic function. METHODS: Thirty-five patients with single-vessel coronary artery diseaseand no previous myocardial infarction were selected. Left andright ventricular filling pressures were monitored by Dopplerechocardiography and haemodynamic monitoring. This was performedduring and immediately after 60 s of coronary balloon occlusionof the left anterior descending artery in 21 cases (Group 1),the left circumflex artery in eight cases (Group 2) and theright coronary artery in six cases (Group 3). Doppler analysisof left and right ventricular filling included peak velocityof early (PFVE) and late ventricular filling (PFVA) and PFVEto PFVA ratio (PFVE/PFVA). RESULTS: In all three groups, balloon inflation induced a significantincrease in left and right filling pressures (P<0·05).No qualitative difference in haemodynamic changes was foundbetween groups during inflation. Significant impairment in theDoppler pattern of left and right ventricular filling occurredafter 20 s of coronary occlusion: PFVE values in mitral andtricuspid valves decreased by 14% and 25% in Group 1, 13% and25% in Group 2, and 10% and 21% in Group 3, respectively. AsPFVA remained unchanged in all groups, the PFVE/PFVA ratio ofmitral and tricuspid valve flows significantly decreased (Group1: –12% and –20%, Group 2: –10% and –21%,Group 3: –14 and –21%, respectively). All parametersreturned to baseline within 30 s after each balloon deflation. CONCLUSION: Our data suggest that brief episodes of acute myocardial ischaemia,such as those induced by 60 s of coronary artery occlusion duringpercutaneous transluminal coronary angioplasty, elicit simultaneousdiastolic dysfunction of both ventricles, independent of thecoronary artery involved.     

Mouse Sebox homeobox gene expression in skin, brain, oocytes, and two-cell embryos

Sebox is a mouse paired-like homeobox gene, previously named OG-9. Sebox genomic DNA and cDNA were cloned and sequenced. In addition, rat and human Sebox genomic DNAs were cloned and sequenced, and the predicted amino acid sequences were compared. The mouse Sebox gene was mapped to chromosome 11 near the Evi 2 locus. The mouse Sebox gene is expressed in brain, skin, ovary, and liver of mice. In the brain, the Sebox gene is expressed in the cerebral cortex and CA areas of the hippocampus, pontine nuclei, choroid plexus, and the cerebellum. Northern analysis and RNase protection assays revealed low levels of Sebox RNA in 12-day mouse embryos and higher levels in 18- and 19-day embryos. In late embryos and newborn mice, Sebox expression is localized in the epidermis. In adult mice, Sebox RNA was found in maturing oocytes and in fertilized eggs; however, the abundance of Sebox RNA is decreased in the two-cell embryo, and little or none was detected in the four-cell embryo. Hence, Sebox is a maternally expressed homeobox gene.     

同源盒基因在胃肠道发育与胃肠道肿瘤发生中的作用

同源盒基因分为HOX基因和Para-HOX基因两大类。作为一类高度保守的基因家族,其在胚胎发育过程中发挥了重要作用;近年来它与肿瘤的关系也受到越来越多的关注。此文对同源盒基因在胃肠道发育及胃肠道肿瘤发生中的作用作一综述。     

The RNA binding protein CPEB regulates dendrite morphogenesis and neuronal circuit assembly in vivo

Visual system development requires experience-dependent mechanisms that regulate neuronal structure and function, including dendritic arbor growth, synapse formation, and stabilization. Although RNA binding proteins have been shown to affect some forms of synaptic plasticity in adult animals, their role in the development of neuronal structure and functional circuitry is not clear. Using two-photon time-lapse in vivo imaging and electrophysiology combined with morpholino-mediated knockdown and expression of functional deletion mutants, we demonstrate that the mRNA binding protein, cytoplasmic polyadenylation element binding protein1 (CPEB1), affects experience-dependent neuronal development and circuit formation in the visual system of Xenopus laevis. These data indicate that sensory experience controls circuit development by regulating translational activity of mRNAs.