Robert Kelly

Publications (4)17.99 Total impact

• Source

  Available from: Saverio Bellusci

  Article: Corrigendum to "Localization and fate of Fgf10-expressing cells in the adult mouse brain implicate Fgf10 in control of neurogenesis" [Mol. Cell. Neurosci. 37 (2008) 857-868].

  Mohammad K Hajihosseini, Stijn De Langhe, Eva Lana-Elola, Harris Morrison, Neil Sparshott, Robert Kelly, James Sharpe, David Rice, Saverio Bellusci
  Molecular and Cellular Neuroscience 11/2009; · 3.66 Impact Factor
• Source

  Available from: Stijn De Langhe

  Article: Localization and fate of Fgf10-expressing cells in the adult mouse brain implicate Fgf10 in control of neurogenesis.

  Mohammad K Hajihosseini, Stijn De Langhe, Eva Lana-Elola, Harris Morrison, Neil Sparshott, Robert Kelly, James Sharpe, David Rice, Saverio Bellusci
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  ABSTRACT: We used Fgf10-lacZ reporter mice to investigate the distribution and fate of Fgf10-expressing cells in the developing and adult mouse brain. We find that the domain of Fgf10 expression expands post-natally and new niches emerge in the adult brain. Fgf10 is expressed in the adult cerebellum, thalamic, mid- and hindbrain nuclei and hippocampal CA fields, as previously reported in the rat brain. In addition though, we have discovered expression in: the hippocampal dentate gyrus; a discrete trail linking the ventral telencephalon with the olfactory bulbs; ventral ependyma of the third ventricle from where cells appear to disperse into the hypothalamus; and in the pituitary gland. Most Fgf10-expressing cells or their immediate descendants appear immature but a subset differentiates into neurons and glial cells. The manner in which Fgf10 is expressed in these active and quiescent neurogenic niches implicates it in control of neurogenesis and/or conservation of neurogenic potential.
  Molecular and Cellular Neuroscience 05/2008; 37(4):857-68. · 3.66 Impact Factor
• Source

  Available from: Stijn De Langhe

  Article: Fgf10 dosage is critical for the amplification of epithelial cell progenitors and for the formation of multiple mesenchymal lineages during lung development.

  Suresh K Ramasamy, Arnaud A Mailleux, Varsha V Gupte, Francisca Mata, Frédéric G Sala, Jacqueline M Veltmaat, Pierre M Del Moral, Stijn De Langhe, Sara Parsa, Lisa K Kelly, Robert Kelly, Wei Shia, Eli Keshet, Parviz Minoo, David Warburton, Savério Bellusci
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  ABSTRACT: The key role played by Fgf10 during early lung development is clearly illustrated in Fgf10 knockout mice, which exhibit lung agenesis. However, Fgf10 is continuously expressed throughout lung development suggesting extended as well as additional roles for FGF10 at later stages of lung organogenesis. We previously reported that the enhancer trap Mlcv1v-nLacZ-24 transgenic mouse strain functions as a reporter for Fgf10 expression and displays decreased endogenous Fgf10 expression. In this paper, we have generated an allelic series to determine the impact of Fgf10 dosage on lung development. We report that 80% of the newborn Fgf10 hypomorphic mice die within 24 h of birth due to respiratory failure. These mutant mouse lungs display severe hypoplasia, dilation of the distal airways and large hemorrhagic areas. Epithelial differentiation and proliferation studies indicate a specific decrease in TTF1 and SP-B expressing cells correlating with reduced epithelial cell proliferation and associated with a decrease in activation of the canonical Wnt signaling in the epithelium. Analysis of vascular development shows a reduction in PECAM expression at E14.5, which is associated with a simplification of the vascular tree at E18.5. We also show a decrease in alpha-SMA expression in the respiratory airway suggesting defective smooth muscle cell formation. At the molecular level, these defects are associated with decrease in Vegfa and Pdgfa expression likely resulting from the decrease of the epithelial/mesenchymal ratio in the Fgf10 hypomorphic lungs. Thus, our results indicate that FGF10 plays a pivotal role in maintaining epithelial progenitor cell proliferation as well as coordinating alveolar smooth muscle cell formation and vascular development.
  Developmental Biology 08/2007; 307(2):237-47. · 4.07 Impact Factor
• Source

  Available from: Saverio Bellusci

  Article: Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage.

  Arnaud A Mailleux, Robert Kelly, Jacqueline M Veltmaat, Stijn P De Langhe, Stephane Zaffran, Jean Paul Thiery, Saverio Bellusci
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  ABSTRACT: Lineage formation in the lung mesenchyme is poorly understood. Using a transgenic mouse line expressing LacZ under the control of Fgf10 regulatory sequences, we show that the pool of Fgf10-positive cells in the distal lung mesenchyme contains progenitors of the parabronchial smooth muscle cells. Fgf10 gene expression is slightly repressed in this transgenic line. This allowed us to create a hypomorphic Fgf10 phenotype by expressing the LacZ transgene in a heterozygous Fgf10 background. Hypomorphic Fgf10 mutant lungs display a decrease in beta-galactosidase-positive cells around the bronchial epithelium associated with an accumulation of beta-galactosidase-expressing cells in the distal mesenchyme. This correlates with a marked reduction of alpha smooth muscle actin expression, thereby demonstrating that FGF10 is mostly required for the entry of mesenchymal cells into the parabronchial smooth muscle cell lineage. The failure of exogenous FGF10 to phosphorylate its known downstream targets ERK and AKT in lung mesenchymal cultures strongly suggests that FGF10 acts indirectly on the progenitor population via an epithelial intermediate. We provide support for a role of epithelial BMP4 in mediating the formation of parabronchial smooth muscle cells.
  Development 06/2005; 132(9):2157-66. · 6.60 Impact Factor