ORCID Profile
0000-0002-8845-2559
Current Organisation
University of California, Irvine
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Publisher: The Company of Biologists
Date: 2015
DOI: 10.1242/DEV.109173
Abstract: Lipid-containing alveolar interstitial fibroblasts, or simply lipofibroblasts, are increasingly recognized as an important component of the epithelial stem-cell niche in the rodent lung. Although lipofibroblasts were initially believed to merely assist type 2 alveolar epithelial cells in surfactant production during neonatal life, recent evidence suggests that these cells are indispensable for the survival and growth of epithelial stem cells during adult life. Despite the increasing interest in lipofibroblast biology, little is known about their cellular origin or the molecular pathways controlling their formation during embryonic development. Here, we show that a population of lipid-droplet-containing stromal cells emerges in the developing mouse lung between E15.5 and E16.5. This event is accompanied by significant upregulation, in the lung mesenchyme, of peroxisome proliferator-activated receptor gamma (the master switch of lipogenesis), adipose differentiation-related protein (marker of mature lipofibroblasts) and fibroblast growth factor 10 (previously shown by our group to identify a subpopulation of lipofibroblast progenitors). We also demonstrate that although only a subpopulation of total embryonic lipofibroblasts derives from Fgf10-positive progenitor cells, in vivo knockdown of Fgfr2b ligand activity as well as reduction in Fgf10 expression lead to global reduction in the expression levels of lipofibroblast markers at E18.5. Constitutive Fgfr1b knockouts and mutants with conditional partial inactivation of Fgfr2b in the lung mesenchyme reveal the involvement of both receptors in lipofibroblast formation and suggest a possible compensation between the two receptors. We also provide data from human fetal lungs to demonstrate the relevance of our discoveries to humans. Our results reveal an essential role for Fgf10 signaling in the formation of lipofibroblasts during late lung development.
Publisher: eLife Sciences Publications, Ltd
Date: 11-07-2017
DOI: 10.7554/ELIFE.22772
Abstract: The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 09-2023
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-03-2023
Abstract: Lateral flight membranes, or patagia, have evolved repeatedly in erse mammalian lineages. While little is known about patagium development, its recurrent evolution may suggest a shared molecular basis. By combining transcriptomics, developmental experiments, and mouse transgenics, we demonstrate that lateral Wnt5a expression in the marsupial sugar glider ( Petaurus breviceps ) promotes the differentiation of its patagium primordium. We further show that this function of Wnt5a reprises ancestral roles in skin morphogenesis predating mammalian flight and has been convergently used during patagium evolution in eutherian bats. Moreover, we find that many genes involved in limb development have been redeployed during patagium outgrowth in both the sugar glider and bat. Together, our findings reveal that deeply conserved genetic toolkits contribute to the evolutionary transition to flight in mammals.
No related grants have been discovered for Maksim Plikus.