Knowing left from right: the molecular basis of laterality defects

The apparent symmetry of the vertebrate body conceals profound asymmetries in the development and placement of internal organs. Asymmetric organ development is controlled in part by genes expressed asymmetrically in the early embryo, and alterations in the activities of these genes can result in severe defects during organogenesis. Recently, data from different vertebrates have allowed researchers to put forward a model of genetic interactions that explains how asymmetric patterns of gene expression in the early embryo are translated into spatial patterns of asymmetric organ development. This model helps us to understand the molecular basis of a number of congenital malformations in humans.     

Somite formation: where left meets right

Somites are the bilaterally symmetric embryonic precursors of the vertebrate skeleton and axial muscle. Three recent studies reveal that somites form asymmetrically in the absence of retinoic acid signaling. These results uncover an unexpected relationship between somitogenesis and left-right patterning, and suggest that bilateral somite formation is regulated along the left-right axis.     

Brain asymmetry: switching from left to right

The relationship between structural and functional asymmetries in the brain remains unclear. A recent report describes a zebrafish mutant that provides us with some enticing clues about this relationship.     

Synergism between the canine left and right hemidiaphragms.

Expansion of the lung during inspiration results from the coordinated contraction of the diaphragm and several groups of rib cage muscles, and we have previously shown that the changes in intrathoracic pressure generated by the latter are essentially additive. In the present studies, we have assessed the interaction between the right and left hemidiaphragms in anesthetized dogs by comparing the changes in airway opening pressure (DeltaPao) obtained during simultaneous stimulation of the two phrenic nerves (measured DeltaPao) to the sum of the DeltaPao values produced by their separate stimulation (predicted DeltaPao). The measured DeltaPao was invariably greater than the predicted DeltaPao, and the ratio between these two values increased gradually as the stimulation frequency was increased; the ratio was 1.10 +/- 0.01 (P < 0.05) for a frequency of 10 Hz, whereas for a frequency of 50 Hz it amounted to 1.49 +/- 0.05 (P < 0.001). This interaction remained unchanged after the rib cage was stiffened and its compliance was made linear, thus indicating that the load against which the diaphragm works is not a major determinant. However, radiographic measurements showed that stimulation of one phrenic nerve extends the inactive hemidiaphragm toward the sagittal midplane and reduces the caudal displacement of the central portion of the diaphragmatic dome. As a result, the volume swept by the contracting hemidiaphragm is smaller than the volume it displaces when the contralateral hemidiaphragm also contracts. These observations indicate that 1) the left and right hemidiaphragms have a synergistic, rather than additive, interaction on the lung; 2) this synergism operates already during quiet breathing and increases in magnitude when respiratory drive is greater; and 3) this synergism is primarily related to the configuration of the muscle.     

Marijuana: Differential effects on right and left hemisphere functions in man

Marijuana, smoked at moderate doses, produced a differential impairment of the reaction times of right-handed males to pictorial stimuli presented to the left and right cerebral hemispheres. After smoking marijuana responses to pictorial stimuli presented to the right hemisphere were slowed significantly less than to the left hemisphere. Responses to verbal stimuli (trigrams) were slowd equally in both hemispheres, preserving an initial left hemisphere superiority for this material. This suggests that marijuana may differentially change the processing speed or relative dominance of man's two cerebral hemispheres, depending on the nature of the material being processed.     

Dissociation between the activity of the right middle frontal gyrus and the middle temporal gyrus in processing semantic priming

The aim of this event-related functional magnetic resonance imaging (fMRI) study was to test whether the right middle frontal gyrus (MFG) and middle temporal gyrus (MTG) would show differential sensitivity to the effect of prime-target association strength on repetition priming. In the experimental condition (RP), the target occurred after repetitive presentation of the prime within an oddball design. In the control condition (CTR), the target followed a single presentation of the prime with equal probability of the target as in RP. To manipulate semantic overlap between the prime and the target both conditions (RP and CTR) employed either the onomatopoeia "oink" as the prime and the referent "pig" as the target (OP) or vice-versa (PO) since semantic overlap was previously shown to be greater in OP. The results showed that the left MTG was sensitive to release of adaptation while both the right MTG and MFG were sensitive to sequence regularity extraction and its verification. However, dissociated activity between OP and PO was revealed in RP only in the right MFG. Specifically, target "pig" (OP) and the physically equivalent target in CTR elicited comparable deactivations whereas target "oink" (PO) elicited less inhibited response in RP than in CTR. This interaction in the right MFG was explained by integrating these effects into a competition model between perceptual and conceptual effects in priming processing.     

RNA kink turns to the left and to the right

A helix-loop-helix within the group I intron has most of the canonical sequence elements of a kink turn (K-turn), yet it bends in the opposite direction. The reverse K-turn kinks toward the major rather than the minor grooves of the flanking helices. This suggests that there are two distinct subclasses of tertiary structures that a K-turn secondary structure can adopt. The final structure may be specified by external factors, such as protein binding or the tertiary structural context, rather than the intrinsic conformation of the RNA.     

Mechanisms of left-right asymmetry: what's right and what's left?

A recent meeting at the Juan March Foundation in Madrid, Spain, covered current understanding of the pathways and mechanisms involved in generating left-right asymmetry.     

Polymorphism and conformational flexibility of DNA: right and left handed duplexes

Left handed duplexes are shown to be in agreement with the X-ray intensity data of A-, B- and D-forms of DNA. The structures are stereochemically satisfactory because they were obtained following a stereochemical guideline derived from theory and single crystal structure data of nucleic acid components. The same stereochemical guideline also led to right handed duplexes for B- and D-forms of DNA which have stereochemically preferred conformation and hence are superior to those given by Arnott and coworkers^10,11.