Search

The left-right symmetry in mammals is broken by a mechanically driven leftward flow of liquid at the embryonic node (nodal flow). A series of elegant embryo culture experiments have clearly demonstrated that an artificial nodal flow can direct the nodal signaling cascade to either the left-side or right side of the embryo.

Nodal activity in the node is discussed relative to its governing of left-right asymmetry. a genetic strategy was used to selectively remove Nodal activity from the node and embryos without it were found not to initiate molecular asymmetry in the left lateral plate mesoderm and to have multiple left-right patterning defects. The study results show that the mouse node is instrumental in initiating left-right axis specification and they show Nodal to be the key regulating morphogen in the process.

Node-specific and asymmetric nodal expression patterns are regulated by two cis-acting regulatory elements distinct from one another. The cis-regulatory elements that control nodal (ital) expression domains in early development have been analyzed. Regulatory sequences that confer node-specific expression are in an upstream region of the locus. Early expression in the epiblast and endoderm and asymmetric expression at later stages on the left side of the axis of the body are controlled by a 600-bp intronic enhancer. Developmentally regulated nodal (ital) expression at certain tissue locations in left-right (L-R) and anterior-posterior (A-P) formation is potentially controlled by shared transcriptional activators.

The bicoid-related homeodomain transcription factor Pitx2 could be the regulatory force behind the gene network responsible for the morphological events that lead to left-right asymmetries in vertebrates. Pitx2 could interpret and later execute the left-right developmental program dictated by upstream signalling molecules. Pitx2 expression is initiated at the onset of organogenesis and maintained throughout embryogenesis. Its left-right instructive role is required both for the heart and for correct situs of the gut and body rotation.

Studies of the mouse Xist gene suggest that methylation controls Xist expression. The unmethylated paternal Xist allele is retained in mature sperm cells leading to paternal Xist allele expression. Differential methylation of Xist alleles are observed in differentiating embryonic stem cells during the triggering of X inactivation.

Abstract The clockwise rotation of cilia in the developing mammalian embryo drives a leftward flow of liquid; this genetically regulated biophysical force specifies left-right asymmetry of the mammalian body. How leftward flow is interpreted and information propagated to other tissues is the subject of debate. Four recent papers have shed fresh light on the possible mechanisms.

Research has been conducted on cell fate decisions. Results demonstrate that these decisions are governed by graded Noda1/Smad2 signals, and that Smad2-dependent signals regulate the formation of PCP precursor populations and the definitive endoderm.

Nodal, a TGF[Beta] signaling molecule, is required in the early mouse embryo for anterior specification, primitive streak formation and has been strongly implicated in left/right determination. Consistent with this function nodal expression is seen in the primitive visceral endoderm (VE) prior to gastrulation; in the epiblast both prior and subsequent to the initiation of gastrulation; in the periphery of the node; and asymmetrically in the left lateral plate mesoderm (11pm) between the 3 and 6 somite stages. Previously we identified a node specific and an intronic enhancer, together recapitulating all four expression domains of nodal (Norris and Robertson, 1999). The intronic enhancer contains putative FAST binding sites (responsive to TGF[Beta]/activin/nodal signaling), likely reflecting autoregulation of the locus. We have now mapped additional enhancers driving nodal expression. We propose a model whereby one enhancer initiates asymmetric expression which is potentiated by the intronic enhancer previously described. We have deleted the intronic enhancer by homologous recombination. Analysis of an allelic series reveals effects of nodal signaling on both the initiation and maintenance of gastrulation and on the establishment of left/right asymmetry.

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. 'Better Experimental Approaches to Treat Primary Ciliary Dyskinesia' (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU Framework Programme Horizon 2020 funded COST Action (BM1407). The Inaugural Conference of BEAT-PCD was held in December 2015 in Southampton, UK. The conference attracted ninety-six scientists, clinicians, allied health professionals, industrial partners and patient representatives from twenty countries. We aimed to identify the needs for PCD research and clinical care, particularly focussing on basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. This allowed us to develop plans for collaborative studies. In this report, we summarize the meeting, highlight developments, and discuss open questions thereby documenting ongoing developments in the field of PCD research. [ABSTRACT FROM AUTHOR]