Gene expression studies of pregastrulation development: the basement membrane is essential for cell differentiation
Author
Summary, in English
EBs derived form embryonic stem (ES) cells, modified to repress FGF receptor signaling, have been described before. However, a full-scale analysis of the transcriptome was missing. We therefore analysed these EBs at four time points during differentiation by the use of microarray technique. An extensive catalogue of affected genes was reported. A majority of the genes directed by FGF signalling were encoding BM and endodermal proteins. In addition, we also analysed the expression profile of wild type EBs. In both these studies, we found interesting genes not previously described in early development or identified as FGF targets. Hopefully, our gene catalogue will be a valuable source for the scientific community interested in FGF signaling, developmental biology and stem cell research. Furthermore, a gene expression study was set up to get a better insight of epiblast inducement by α1LG4-5. EBs derived form ES cells with a targeted deletion of the α1LG4-5 domains were analysed. To our surprise, we found several indications of an incomplete differentiation of the visceral endoderm. We therefore hypothesize a novel autocrine mechanism for α1LG4-5 in regulating the developing endoderm.
We also suggest novel roles for laminin LG4-5 in the neuromuscular system. Using laminin α2 chain deficient mice overexpressing laminin α1 chain lacking the LG4-5 domains, we show that these domains, and consequently binding to the receptor dystroglycan are not crucial in diaphragm and heart, but essential in the peripheral nervous system.
Department/s
Publishing year
2009
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2009:92
Full text
- Available as PDF - 406 kB
- Download statistics
Document type
Dissertation
Publisher
Department of Experimental Medical Science, Lund Univeristy
Topic
- Cell and Molecular Biology
Keywords
- muscular dystrophy
- development
- Basement membrane
- laminin
- stem cells
- FGF
Status
Published
Research group
- Muscle Biology
Supervisor
- Madeleine Durbeej-Hjalt
- Susanne Schéele
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-86253-81-3
Defence date
13 January 2010
Defence time
13:00
Defence place
Segerfalksalen, BMC, Sölvegatan 17, Lund
Opponent
- Manuel Patarroyo (Professor)