The term ramogen refers to a biological factor, typically a growth factor or other protein, that causes a developing biological cell or tissue to branch in a tree-like manner. Ramogenic molecules are branch promoting molecules found throughout the human body.Davies, J. A., & Davey, M. G. (1999). Collecting duct morphogenesis. Pediatric Nephrology, 13(6), 535-541.
Brief History
The term was first coined (from the Latin ramus = branch and the Greek genesis = creation) in an article about kidney development by Davies and Davey (Pediatr Nephrol. 1999 Aug;13(6):535-41). In the article, Davies and Davy describe the existence of "ramogens" in the kidney as glial cell line-derived neurotrophic factors, neurturin and persephin.Davies, J. A., & Davey, M. G. (1999). Collecting duct morphogenesis. Pediatric Nephrology, 13(6), 535-541. The term has now passed into general use in the technical literature concerned with branching of biological structures.
Function A ramogen is a biochemical signal that enables the creation of a physiological branch. The signal can be in the form of a growth factor or a hormone that makes a tube branch. One specific example would be the hormone that forms the simple tube through which the mammary glands begin to form causing the formation of a highly branched “tree” of milk ducts in females.Davies, J.A. (2005). Mechanisms of Morphogenesis: the creation of biological form. Burlington, MA: Elsevier Inc.
Types of Ramogens
Mesenchyme-derived ramogens are found throughout the body and serve as chemoattractants to branching tissues. An example of how this works is found through a study on a bead soaked in the renal ramogen GDNF. When this ramogen was placed next to a kidney sample in culture, the nearby uteric parts branch and grow toward it.Davies, J.A. (2005). Mechanisms of Morphogenesis: the creation of biological form. Burlington, MA: Elsevier Inc.
Another example of a ramogen in use was found in the lungs. The existence of Sprouty2 in the body is demonstrated in response to the signaling of the ramogen FGF10, serving as an inhibitor of branching.Davies, J.A. (2005). Mechanisms of Morphogenesis: the creation of biological form. Burlington, MA: Elsevier Inc.
The following table is a list of Key Ramogens in Branching Organs of a mouse species.Davies, J.A. (2005). Mechanisms of Morphogenesis: the creation of biological form. Burlington, MA: Elsevier Inc.
Branching System Main Paracrine Ramogen Trachae in D. melanogaster Branchless (FGF homologue) via breathless (FGFR homologue Lung FGF10 via FGFRIIIb Pancreas FGF10 via FGFRIIIb Mammary Gland FGF7 via FGFRIIIb Kidney GDNF via FGRa1-Ret-complex Prostate FGF7 via FGFRIIIb
Studies involving Ramogens
The physiological capabilities of ramogens are still being postulated in medical studies involving kidney functions on mice.
In development maturing nephrons and stroma in the body may cease to produce ramogens and may begin to secrete anti-ramogenic factors, such as Bmp2 and Tgfβ.Sweeney, D., Lindstrom, N. and Davies, L. (2008). Developmental plasticity and regenerative capacity in the renal ureteric bud/collecting duct system. Development, 135, 2505-2010
The pattern of branching and the rate of cell proliferation can contribute to the shape of different organs. As such, the use of the glial-cell-line neurotrophic factor (GDNF) has been found to contribute to uterine tissues.Sakurai, H., Bush, K. T. and Nigam, S. K. (2001). Identification of pleiotrophin as a mesenchymal factor involved in ureteric bud branching morphogenesis. Development128,3283 -3293.
The implication of this is that the introduction of ramogens to the body can cause cell repair through the creation of side branches introduced through ramogenic signals in the body Davies, J. A., & Davey, M. G. (1999). Collecting duct morphogenesis. Pediatric Nephrology, 13(6), 535-541. ).
This is evidenced through studies demonstrating that uterine stalks were capable of forming new tips if provided with fresh mesenchyme or with a Matrigel artificially loaded with ramogens, such as GDNF and FGF1. The ramogens used in this study were manufactured with fresh mesenchyme.Suvanto, P., Davies, J., Wartiovaara, J., Wartiovaara, K., Saarma, M., Arumae, U., Meng, X., Lindahl, M., Pachnis, V. et al. (1997). Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium. Development124,4077 -4087.