title: mTOR signalling, embryogenesis and the control of lung development.
abstract: The existence of a nutrient sensitive "autocatakinetic" regulator of embryonic tissue growth has been hypothesised since the early 20th century, beginning with pioneering work on the determinants of foetal size by the Australian physiologist, Thorburn Brailsford-Robertson. We now know that the mammalian target of rapamycin complexes (mTORC1 and 2) perform this essential function in all eukaryotic tissues by balancing nutrient and energy supply during the first stages of embryonic cleavage, the formation of embryonic stem cell layers and niches, the highly specified programmes of tissue growth during organogenesis and, at birth, paving the way for the first few breaths of life. This review provides a synopsis of the role of the mTOR complexes in each of these events, culminating in an analysis of lung branching morphogenesis as a way of demonstrating the central role mTOR in defining organ structural complexity. We conclude that the mTOR complexes satisfy the key requirements of a nutrient sensitive growth controller and can therefore be considered as Brailsford-Robertson's autocatakinetic centre that drives tissue growth programmes during foetal development.
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. Electronic address: scland@dundee.ac.uk.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Land
authors.affiliation: Prostrakan Pharmaceuticals, Galabank Business Park, Galashiels TD1 1PR, UK.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Scott
authors.affiliation: School of Psychology & Neuroscience, Westburn Lane, St Andrews KY16 9JP, UK.
authors.forename: David
authors.initials: D
authors.lastname: Walker
mesh_terms: D054262:Gastrulation / Q000502:physiology; D006801:Humans; D008168:Lung / Q000196:embryology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D038081:Organogenesis / Q000502:physiology*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases
keywords: Branching morphogenesis; Cardio-pulmonary system; Embryonic growth; Fertilisation; Hypoxia inducible factor; Sprouty2