title: Cellular and molecular drivers of differential organ growth: insights from the limbs of Monodelphis domestica.
abstract: A fundamental question in biology is "how is growth differentially regulated during development to produce organs of particular sizes?" We used a new model system for the study of differential organ growth, the limbs of the opossum (Monodelphis domestica), to investigate the cellular and molecular basis of differential organ growth in mammals. Opossum forelimbs grow much faster than hindlimbs, making opossum limbs an exceptional system with which to study differential growth. We first used the great differences in opossum forelimb and hindlimb growth to identify cellular processes and molecular signals that underlie differential limb growth. We then used organ culture and pharmacological addition of FGF ligands and inhibitors to test the role of the Fgf/Mitogen-activated protein kinases (MAPK) signaling pathway in driving these cellular processes. We found that molecular signals from within the limb drive differences in cell proliferation that contribute to the differential growth of the forelimb and hindlimbs of opossums. We also found that alterations in the Fgf/MAPK pathway can generate differences in cell proliferation that mirror those observed between wild-type forelimb and hindlimbs of opossums and that manipulation of Fgf/MAPK signaling affects downstream focal adhesion-extracellular matrix (FA-ECM) and Wnt signaling in opossum limbs. Taken together, these findings suggest that evolutionary changes in the Fgf/MAPK pathway could help drive the observed differences in cell behaviors and growth in opossum forelimb and hindlimbs.
authors.affiliation: School of Integrative Biology, University of Illinois, 505 S Goodwin Avenue, Urbana, IL, 61801, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Dowling
authors.affiliation: School of Integrative Biology, University of Illinois, 505 S Goodwin Avenue, Urbana, IL, 61801, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Doroba
authors.affiliation: School of Integrative Biology, University of Illinois, 505 S Goodwin Avenue, Urbana, IL, 61801, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Maier
authors.affiliation: School of Integrative Biology, University of Illinois, 505 S Goodwin Avenue, Urbana, IL, 61801, USA.
authors.forename: Lorna
authors.initials: L
authors.lastname: Cohen
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: VandeBerg
authors.affiliation: School of Integrative Biology, University of Illinois, 505 S Goodwin Avenue, Urbana, IL, 61801, USA. ksears@life.illinois.edu.|Institute for Genomic Biology, University of Illinois, 1206 W Gregory Drive, Urbana, IL, 61801, USA. ksears@life.illinois.edu.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Sears
mesh_terms: D000818:Animals; D016923:Cell Death; D049109:Cell Proliferation; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005552:Forelimb / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D006614:Hindlimb / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D048309:Monodelphis / Q000254:growth & development* / Q000378:metabolism
chemical_list: D005346:Fibroblast Growth Factors
keywords: Cell death; Cell proliferation; FA-ECM signaling; Fgf signaling; Opossum; Wnt signaling