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Developmental cooperation of leukemia inhibitory factor and insulin-like growth factor I in mice is tissue-specific and essential for lung maturation involving the transcription factors Sp3 and TTF-1

Pichel, Jose G. and Fernández-Moreno, Carmen and Vicario-Abejón, Carlos and Testillano, Pilar S. and Patterson, Paul H. and de Pablo, Flora (2003) Developmental cooperation of leukemia inhibitory factor and insulin-like growth factor I in mice is tissue-specific and essential for lung maturation involving the transcription factors Sp3 and TTF-1. Mechanisms of Development, 120 (3). pp. 349-361. ISSN 0925-4773. https://resolver.caltech.edu/CaltechAUTHORS:20160122-105355199

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Abstract

The multifunctional proteins leukemia inhibitory factor (LIF) and insulin-like growth factor I (IGF-I) are expressed in overlapping patterns during development and, therefore, may act cooperatively. We show that mice doubly deficient in LIF and IGF-I all died at birth of apparent respiratory failure. Growth retardation, muscle hypoplasia and delayed ossification in IGF-I-deficient E18.5 mice were exacerbated by the absence of LIF. The transcription factor Sp3 was decreased in the skeleton of the double null mice. Pronounced depletion of olfactory bulb neurons, in contrast, was only IGF-I-dependent. The lungs displayed reduced air space in the IGF-I-deficient embryos and neonates, phenotype exacerbated in the double nulls, which showed abnormal epithelial cells and decreased Sp3 expression. In addition, the transcription factor TTF-1 and the surfactant protein B were lower in the lung of the double null neonates than in all other genotypes. LIF and IGF-I, thus, have cooperative and distinct tissue functions during development. Their essential role in bone ossification apparently involves Sp3, and in lung maturation Sp3 together with TTF-1.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/S0925-4773(02)00449-5DOIArticle
http://www.sciencedirect.com/science/article/pii/S0925477302004495PublisherArticle
Additional Information:© 2002 Elsevier Science Ireland Ltd. Received 6 August 2002; received in revised form 24 September 2002; accepted 15 November 2002. We thank A. Efstratiadis and C.L. Stewart for providing the targeted mice to establish a breeding program as well as IGF-I and LIF probes, and R. Di Lauro (Stazione Zoologica, Naples, Italy) for the TTF-1 probe and J. Floros (Pennsylvania State University, Hershey, PA) for the SP-B probe (both provided through Pilar Santisteban, IIB, CSIC). We are grateful to E.J. de la Rosa and C. Hernández-Sánchez for insightful comments on the work and the manuscript and to J.L. Jorcano, J. Paramio, J. Moreno and M.C. Risueño for help with histopathological interpretation. This study was funded by grants PM 97-0143 and BMC 2001-2132 from the MEC and MCYT (Spain) to F. de P. J.G.P. and C.V.-A. are investigators of the Programa Ramόn y Cajal and C.F.-M. is a doctoral fellow from the MCYT (Spain).
Funders:
Funding AgencyGrant Number
Ministerio Ciencia y Tecnología (MCYT)PM 97-0143
Ministerio Ciencia y Tecnología (MCYT)BMC 2001-2132
Programa Ramόn y CajalUNSPECIFIED
Subject Keywords:Development; Double mutant mice; Lung; Ossification; Muscle; Olfactory bulb; Insulin-like growth factor I; Leukemia inhibitory factor; Sp3; TTF-I; Surfactant protein B
Issue or Number:3
Record Number:CaltechAUTHORS:20160122-105355199
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160122-105355199
Official Citation:Jose G. Pichel, Carmen Fernández-Moreno, Carlos Vicario-Abejón, Pilar S. Testillano, Paul H. Patterson, Flora de Pablo, Developmental cooperation of leukemia inhibitory factor and insulin-like growth factor I in mice is tissue-specific and essential for lung maturation involving the transcription factors Sp3 and TTF-1, Mechanisms of Development, Volume 120, Issue 3, March 2003, Pages 349-361, ISSN 0925-4773, http://dx.doi.org/10.1016/S0925-4773(02)00449-5. (http://www.sciencedirect.com/science/article/pii/S0925477302004495)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63891
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:25 Jan 2016 17:25
Last Modified:03 Oct 2019 09:32

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