PLoS Biol 8 6 : e This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: No specific funding was received for this work. Competing interests: The author has declared that no competing interests exist. It does not happen often that an entirely novel gene regulatory mechanism is revealed. The discovery of microRNAs miRNAs is one such finding that revolutionized our understanding of cellular events and of the intricacy of developmental processes [1] , [2].

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Abstract Robustness is a fundamental property of biological systems. Here, we discuss the roles that microRNAs play in providing canalization to animal development, citing recent theoretical and experimental advances. MicroRNAs repress protein expression, and they do this in ways that create thresholds in expression and provide adaptation to regulatory networks. Numerous examples have now been described where the developmental impact of environmental variation is suppressed by individual microRNAs.

A recent paper has found that the impact of genomic variation between individuals is similarly suppressed by a microRNA operating in a developmental network. Thus, genetic variability is held in check, which is potentially important for both animal evolution and manifestation of disease.

Organisms are naturally subject to fluctuating environments, and yet their morphological development is generally robust to such challenges. Indeed, robustness is a universal emergent property of living systems. The inverse relationship between developmental robustness and morphological variation in natural populations has long been remarked upon [ 1 ], and Waddington coined the word canalization to describe the process [ 2 ].

The stronger the canalization of development, the less phenotypic variation exists among individuals in a population. Canalization also decouples the effects of genomic variation on development, which geneticists have long described by the incomplete penetrance and expressivity of morphological phenotypes [ 3 ]. This genome-suppressing property of canalization has implications for evolutionary mechanisms.

In one sense, canalization should inhibit evolvability since it suppresses the phenotypic variation that selection acts upon Fig. However, if a phenotype is robust to the effects of genome variation, then this variation can accumulate without affecting the phenotype.

When canalization becomes impaired, then this genomic diversity suddenly expresses phenotypic variability, which can be subject to selection, thus potentially accelerating evolvability. There are two routes to impairing canalization. One is to disable by mutation the molecular mechanisms that generate robustness. The other is to overwhelm the canalization apparatus by environmental stress.


Canalization of development by microRNAs

David A. Abstract During development, angiogenesis occurs as a controlled series of events leading to neovascularization that supports changing tissue requirements. Several pro- and antiangiogenic factors orchestrate a complex, dynamic process to allow initial sprouting and invasion, subsequent pruning and remodeling, and finally maturation and survival of blood vessels. In the last decade, a new class of small RNA molecules termed micro-RNAs miRs have emerged as key regulators of several cellular processes including angiogenesis. Micro-RNAs such as miR, miR, miR, miR, and miRa have been shown to play pro- and antiangiogenic roles in the vasculature of both endothelial cells and perivascular cells. However, in pathological situations such as cancer or inflammation, the same angiogenic signaling pathways and miRs are dysregulated and exploited, typically resulting in poorly organized vessels with leaky and tortuous properties. This article is a brief overview of specific miRs that have been reported to play a role in the vasculature.


MicroRNAs and their roles in developmental canalization



Emerging Role of Micro-RNAs in the Regulation of Angiogenesis


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