TY  - JOUR
A1  - Kang, Ji Hyoun
A1  - Manousaki, Tereza
A1  - Franchini, Paolo
A1  - Kneitz, Susanne
A1  - Schartl, Manfred
A1  - Meyer, Axel
T1  - Transcriptomics of two evolutionary novelties: how to make a sperm-transfer organ out of an anal fin and a sexually selected "sword" out of a caudal fin
JF  - Ecology and Evolution
N2  - Swords are exaggerated male ornaments of swordtail fishes that have been of great interest to evolutionary biologists ever since Darwin described them in the Descent of Man (1871). They are a novel sexually selected trait derived from modified ventral caudal fin rays and are only found in the genus Xiphophorus. Another phylogenetically more widespread and older male trait is the gonopodium, an intromittent organ found in all poeciliid fishes, that is derived from a modified anal fin. Despite many evolutionary and behavioral studies on both traits, little is known so far about the molecular mechanisms underlying their development. By investigating transcriptomic changes (utilizing a RNA-Seq approach) in response to testosterone treatment in the swordtail fish, Xiphophorus hellerii, we aimed to better understand the architecture of the gene regulatory networks underpinning the development of these two evolutionary novelties. Large numbers of genes with tissue-specific expression patterns were identified. Among the sword genes those involved in embryonic organ development, sexual character development and coloration were highly expressed, while in the gonopodium rather more morphogenesis-related genes were found. Interestingly, many genes and genetic pathways are shared between both developing novel traits derived from median fins: the sword and the gonopodium. Our analyses show that a larger set of gene networks was co-opted during the development and evolution of the older gonopodium than in the younger, and morphologically less complex trait, the sword. We provide a catalog of candidate genes for future efforts to dissect the development of those sexually selected exaggerated male traits in swordtails.
KW  - mouse testis differentiation
KW  - fishes Xiphophorus
KW  - beetle horns
KW  - gonopodium
KW  - RNA-Seq
KW  - swordtails
KW  - Xiphophorus
KW  - key innovation
KW  - male-specific traits
KW  - Co-option
KW  - genus Xiphophorus
KW  - hybrid origin
KW  - Drosophila melanogaster
KW  - expression analysis
KW  - cell proliferation
KW  - preexisting bias
KW  - sex combs
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144139
VL  - 5
IS  - 4
ER  - 
TY  - JOUR
A1  - Seher, Axel
A1  - Lagler, Charlotte
A1  - Stühmer, Thorsten
A1  - Müller-Richter, Urs Dietmar Achim
A1  - Kübler, Alexander Christian
A1  - Sebald, Walter
A1  - Müller, Thomas Dieter
A1  - Nickel, Joachim
T1  - Utilizing BMP-2 muteins for treatment of multiple myeloma
JF  - PLoS ONE
N2  - Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM. Therefore three BMP2 derivatives were generated with modified binding activities for the type II (ActRIIB) and/or type I receptor (BMPRIA) showing either increased or decreased BMP2 activity. In the context of MM these BMP2 muteins show two functionalities since they act as a) an anti-proliferative/apoptotic agent against neoplastic B-cells, b) as a bone-formation promoting growth factor. The molecular basis of both activities was shown in two different cellular models to clearly rely on the properties of the investigated BMP2 muteins to compete for the binding of Activin A to the Activin type II receptors. The experimental outcome suggests new therapeutic strategies using BMP2 variants in the treatment of MM-related pathologies.
KW  - multiple myeloma
KW  - signaling
KW  - cell proliferation
KW  - cell binding
KW  - membrane receptor signaling
KW  - BMP
KW  - gene expression
KW  - B cell receptors
KW  - B cells
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158144
VL  - 12
IS  - 5
ER  -