We study the molecular genetics of mammalian development. Our interest is focused on developmental controls exerted by LIM-homeodomain (LIM-HD) transcription factors that are encoded by individual members of the Lhx gene family. In the embryo, and also in the adult, Lhx Genes mediate the transit from the stem cell stage to a precursor stage that precedes terminal differentiation. In our earlier experiments, we determined the functions of a number of Lhx genes through loss-of-function analysis of knockout mice, and we described obligatory cofactors, encoded by Ldb and Ssdp genes, respectively, that mediate Lhx gene function. In the work described here, we have adopted regimens of Cre-mediated conditional mutation, originally developed in our laboratory, to ask more fine-tuned questions regarding the action of LIM-HD/cofactor complexes and their downstream Dkk targets as patterns form and organs are established in the developing mouse embryo.

Project Start
Project End
Budget Start
Budget End
Support Year
34
Fiscal Year
2006
Total Cost
Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
Type
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Country
United States
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Gorivodsky, Marat; Mukhopadhyay, Mahua; Wilsch-Braeuninger, Michaela et al. (2009) Intraflagellar transport protein 172 is essential for primary cilia formation and plays a vital role in patterning the mammalian brain. Dev Biol 325:24-32
Storbeck, Chris J; Wagner, Simona; O'Reilly, Paul et al. (2009) The Ldb1 and Ldb2 transcriptional cofactors interact with the Ste20-like kinase SLK and regulate cell migration. Mol Biol Cell 20:4174-82
Backman, Cristina M; Zhang, YaJun; Malik, Nasir et al. (2009) Generalized tetracycline induced Cre recombinase expression through the ROSA26 locus of recombinant mice. J Neurosci Methods 176:16-23
Zhao, Yangu; Flandin, Pierre; Long, Jason E et al. (2008) Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants. J Comp Neurol 510:79-99
Hwang, Minyoung; Gorivodsky, Marat; Kim, Minjung et al. (2008) The neuronal differentiation potential of Ldb1-null mutant embryonic stem cells is dependent on extrinsic influences. Stem Cells 26:1490-5
Ellwanger, Kristina; Saito, Hiroaki; Clement-Lacroix, Philippe et al. (2008) Targeted disruption of the Wnt regulator Kremen induces limb defects and high bone density. Mol Cell Biol 28:4875-82
Lewis, Samara L; Khoo, Poh-Lynn; De Young, R Andrea et al. (2008) Dkk1 and Wnt3 interact to control head morphogenesis in the mouse. Development 135:1791-801
Cheung, Yuk Yin; Kim, So Youn; Yiu, Wai Han et al. (2007) Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta. J Clin Invest 117:784-93
Lewis, Samara L; Khoo, Poh-Lynn; Andrea De Young, R et al. (2007) Genetic interaction of Gsc and Dkk1 in head morphogenesis of the mouse. Mech Dev 124:157-165
Suleiman, Hani; Heudobler, Daniel; Raschta, Anne-Sarah et al. (2007) The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes. Dev Biol 304:701-12

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