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1.  Nephrons require Rho-kinase for proximal-distal polarity development 
Scientific Reports  2013;3:2692.
Epithelial tubules must have the right length and pattern for proper function. In the nephron, planar cell polarity controls elongation along the proximal-distal axis. As the tubule lengthens, specialized segments (proximal, distal etc.) begin to differentiate along it. Other epithelia need Rho-kinase for planar cell polarity but it is not known whether Rho-kinase is involved in this way in the nephron. We show that Rho-kinase is essential for the morphogenesis of nephrons, specifically for correct cell orientation and volume. We use fluorescent reporter-models and progenitor-specific markers to demonstrate that inhibition of Rho-kinase prevents proper proximal-distal axis formation, causes segments to develop abnormally, and progenitor-cell segregation to fail. Our data demonstrate the importance of Rho-kinase in normal nephron tubulogenesis and patterning.
doi:10.1038/srep02692
PMCID: PMC3776198  PMID: 24045698
2.  Tissue specific characterisation of Lim-kinase 1 expression during mouse embryogenesis 
Gene expression patterns : GEP  2010;11(3-4):221-232.
The Lim-kinase (LIMK) proteins are important for the regulation of the actin cytoskeleton, in particular the control of actin nucleation and depolymerisation via regulation of cofilin, and hence may control a large number of processes during development, including cell tensegrity, migration, cell cycling, and axon guidance. LIMK1/LIMK2 knockouts disrupt spinal cord morphogenesis and synapse formation but other tissues and developmental processes that require LIMK are yet to be fully determined. To identify tissues and cell-types that may require LIMK, we characterised the pattern of LIMK1 protein during mouse embryogenesis. We showed that LIMK1 displays an expression pattern that is temporally dynamic and tissue-specific. In several tissues LIMK1 is detected in cell-types that also express Wilms’ tumour protein 1 and that undergo transitions between epithelial and mesenchymal states, including the pleura, epicardium, kidney nephrons, and gonads. LIMK1 was also found in a subset of cells in the dorsal retina, and in mesenchymal cells surrounding the peripheral nerves. This detailed study of the spatial and temporal expression of LIMK1 shows that LIMK1 expression is more dynamic than previously reported, in particular at sites of tissue–tissue interactions guiding multiple developmental processes.
doi:10.1016/j.gep.2010.12.003
PMCID: PMC3407955  PMID: 21167960
Limk; Kidney; Heart; Epithelia-to-mesenchyme transition; Mesenchyme-to-epithelia transition; Eye; Testes
3.  Node retraction during patterning of the urinary collecting duct system 
Journal of Anatomy  2014;226(1):13-21.
This report presents a novel mechanism for remodelling a branched epithelial tree. The mouse renal collecting duct develops by growth and repeated branching of an initially unbranched ureteric bud: this mechanism initially produces an almost fractal form with young branches connected to the centre of the kidney via a sequence of nodes (branch points) distributed widely throughout the developing organ. The collecting ducts of a mature kidney have a different form: from the nephrons in the renal cortex, long, straight lengths of collecting duct run almost parallel to one another through the renal medulla, and open together to the renal pelvis. Here we present time-lapse studies of E11.5 kidneys growing in culture: after about 5 days, the collecting duct trees show evidence of ‘node retraction’, in which the node of a ‘Y’-shaped branch moves downwards, shortening the stalk of the ‘Y’, lengthening its arms and narrowing their divergence angle so that the ‘Y’ becomes a ‘V’. Computer simulation suggests that node retraction can transform a spread tree, like that of an early kidney, into one with long, almost-parallel medullary rays similar to those seen in a mature real kidney.
doi:10.1111/joa.12239
PMCID: PMC4299504  PMID: 25292187
branching morphogenesis; collecting duct; development; modelling; embryonic kidney; organogenesis; pattern formation; ureteric bud

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