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Transforming growth factor beta and mouse development
1Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, The Netherlands. christin@niob.knaw.nl
Abstract:
Transforming growth factor beta has many biological effects including the control of cellular growth, differentiation, migration and extracellular matrix production; these are all processes essential for normal development. Although mice first generated more than eight years ago, bearing mutations in TGF beta ligands demonstrated the importance of TGF beta-induced signal transduction pathways for development in mammals but complete functional analysis is still lacking. Here, the current state-of-the-art in mouse development is reviewed. As a basis for understanding function, the principle features of mouse development over the 21 days of pregnancy are described and illustrated, from fertilization of the egg to mid-gestation when organogenesis is largely complete. This is completed with a description of when and where TGF beta ligands, receptors and downstream signalling molecules are expressed as the mouse embryo develops. The functions of TGF beta in preimplantation development, in implantation of the embryos in the uterine wall and in postimplantation development are then described through a review of the literature on gene ablation of the ligands, receptors and downstream molecules, or the ectopic expression of dominant negative forms of the receptors in vivo, which interfere with normal signal transduction. The evidence confirms multifunctional roles at all stages of development.
Insights
Transforming growth factor beta (TGF-β) is crucial for mammalian development. This review details TGF-β
Area of Science:
- Developmental Biology
- Molecular Biology
- Cell Biology
Background:
- Transforming growth factor beta (TGF-β) regulates critical cellular processes like growth, differentiation, and migration.
- TGF-β signaling pathways are vital for mammalian development, yet their complete functional analysis remains incomplete.
- Mouse models have been instrumental in understanding TGF-β's role, but a comprehensive review is needed.
Purpose of the Study:
- To review the current state-of-the-art in mouse development.
- To describe the temporal and spatial expression of TGF-β ligands, receptors, and signaling molecules during embryogenesis.
- To elucidate the multifunctional roles of TGF-β in preimplantation, implantation, and postimplantation development.
Main Methods:
- Review of existing literature on mouse development.
- Analysis of gene ablation studies for TGF-β ligands, receptors, and downstream molecules.
- Examination of studies using dominant-negative receptor expression in vivo.
- Description of mouse embryonic development from fertilization to mid-gestation.
Main Results:
- TGF-β ligands, receptors, and signaling molecules exhibit specific expression patterns throughout mouse embryogenesis.
- Gene ablation and dominant-negative studies reveal essential roles for TGF-β in preimplantation development.
- TGF-β is critical for successful embryo implantation into the uterine wall.
- Multifunctional roles of TGF-β are confirmed across all stages of postimplantation development, including organogenesis.
Conclusions:
- Transforming growth factor beta (TGF-β) plays indispensable, multifunctional roles throughout mammalian development.
- Understanding TGF-β signaling is key to comprehending normal embryonic development and potential developmental disorders.
- Further research utilizing mouse models will continue to refine our understanding of TGF-β's complex regulatory networks.