Characterization of miRNA processing machinery in the embryonic chick lung

Abstract

Lung development is a very complex process that relies on the interaction of several signaling pathways that are controlled by precise regulatory mechanisms. Recently, microRNAs (miRNAs), small non-coding regulatory RNAs, have emerged as new players involved in gene expression regulation controlling several biological processes, such as cellular differentiation, apoptosis and organogenesis, in both developmental and disease processes. Failure to correctly express some specific miRNAs or a component of their biosynthetic machinery during embryonic development is disastrous, resulting in severe abnormalities. Several miRNAs have already been identified as modulators of lung development. Regarding the spatial distribution of the processing machinery of miRNAs, only two of its members (dicer1 and argonaute) have been characterized. The present work characterizes the expression pattern of drosha, dgcr8, exportin-5 and dicer1 in early stages of the embryonic chick lung by whole mount in situ hybridization and cross-section analysis. Overall, these genes are co-expressed in dorsal and distal mesenchyme and also in growing epithelial regions. The expression pattern of miRNA processing machinery supports the previously recognized regulatory role of this mechanism in epithelial and mesenchymal morphogenesis.

Recent advances in our understanding of the mechanisms of late lung development and bronchopulmonary dysplasia

“…Noncoding RNA. Noncoding RNAs, in particular, microRNAs, have emerged as pivotal regulators of organogenesis, and the lung is almost certainly no exception (26,116,245,368). While the expression of many microRNA species is known to be deregulated in animal models of BPD (570), very few studies have addressed causal roles for microRNA species in normal and aberrant alveolarization (382,384).…”

Retinoic acid regulates avian lung branching through a molecular network

“…Likewise, SHH (sonic hedgehog) signaling members are expressed in chick embryonic lung [7] and their importance in chick lung branching was revealed in talpid 3 mutants that display abnormal (hypoplastic) lung phenotype due to a defective SHH signaling [8]. Other signaling pathways such as microRNAs [9] and TGFβ-BMP (transforming growth factor β-bone morphogenetic protein) signaling [10] have also been characterized in the chick developing lung. Overall these signaling pathways behave similarly to their mammalian counterparts (reviewed in [11]).…”

“…All lung sections were photographed using a camera (Olympus DP70) coupled to a microscope (Olympus BX61). Afterwards, slide sections were stained with hematoxylin-eosin as previously described [9] and photographed again at the same magnification.…”

Hampered Lung Maturation in Methimazole-Induced Hypothyroidism in Fetal Chicken: Morphological and Molecular Correlates to Human Fetal Development

“…Their effects are thus not necessarily cell autonomous and they are likely to be crucial molecules in human development. In the developing lung, the expression of important miR-processing components has recently been characterized [23]. Loss in the lung epithelium of Dicer, the key enzyme for cleaving pre-miRNA into mature miRNA, results in severe lung defects and perinatal lethality with impaired branching and epithelial structure [24].…”