Though every cell is known to be ciliated, in the context of somite, limb and kidney the function of cilia is better characterized. Ong et al PETCM speculated the involvement of flow-sensing cilia, as mediator of ����glomerulo-tubular balance���� in the context of kidney. Glomerulo-tubular balance refers to the phenomenon which ensures that the rate of fluid re-absorption in the proximal renal tubule is always in proportion to the rate of glomerular filtration. This requires the presence of a mechanotransducer which shall transduce the mechanical stimulus of fluid flow into signals regulating transport across ion channels. Indeed Praetorius and Spring through studies on Madin-Darby canine kidney cells, a canine kidney cell line derived from the collecting duct, reported presence of primary cilia in renal epithelium. Their study showed that this cilia is capable of sensing mechanical forces i.e, it bends when suction is applied with micropipette or if the flow rate of perfusate is increased. It also responds to the mechanical stimulus as indicated by increased calcium uptake. Further this response is not restricted to one cell. It propagates throughout the epithelial tissue by cell-cell interaction mediated by calcium signaling at cellular junctions. This was validated using gap junction permeation inhibitor heptanol which resulted in significant reduction in spread of the response. Thus it is very likely that similar to inner ear, renal epithelial cells must have a sensory system capable of sensing the variations in fluid shear stress, amplifying it and transmitting it to the intracellular cytoskeleton and thus mediating the functional regulation of membrane transport proteins. Cdh23 is a good candidate to be involved in this process. The limb expression domain of Cdh23 is very similar to the expression of another gene Papss2 reported in our metabolism Org 24598 lithium salt related genes screen as well as to Sulf1 as reported by Zhao et al. In our MRG screen at HH26 and HH28, Papss2 is expressed in the condensing mesenchyme. Zhao et al through in situ hybridization screen in quail embryos showed that at around HH27, Sulf1 is also expressed in the condensing mesenchyme. In the context of limb skeletal development, mesenchymal cells of the developing limb bud condense and undergo chondrogenesis i.e., differentiation into cartilage fate. This cartilage anlagen serves as the template for bone formation during endochondral ossification. During this process, cartilage cells at the centre of the skeletal element undergo hypertrophic differentiation, followed by matrix secretion and apoptosis. Concomitant to this, vascular, neuronal and osteoblast invasion takes place in this zone followed by ossification which is marked by the formation of bone collar.
Modifications in primary metabolism might have an influence
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