Functional analysis of the T-box transcription factors Tbx2 and Tbx3 in the development of the ureteric mesenchyme in the Mouse
Başlık çevirisi mevcut değil.
- Tez No: 582618
- Danışmanlar: Prof. Dr. ANDREAS KİSPERT
- Tez Türü: Doktora
- Konular: Moleküler Tıp, Molecular Medicine
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2017
- Dil: İngilizce
- Üniversite: Medizinische Hochschule Hannover
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: 101
Özet
Özet yok.
Özet (Çeviri)
The mammalian urinary system is a multi-component entity that is composed of the kidneys, the ureters, the bladder and the urethra. It eliminates the waste products and maintains the homeostasis of the blood, water, pH and ions in the body. These functions depend on the structural and functional integrity of the organs of the urinary system. The ureters are tubular organs that transfer the urine from the kidneys down to the bladder. The development of the ureter highly depends on the reciprocal interaction between the epithelium and the mesenchyme. Signals such as WNT and SHH from the epithelium act on the adjacent mesenchyme to regulate different cellular events in this domain. Canonical Wnt signaling induces smooth muscle differentiation and represses fibroblast formation in the inner mesenchyme of the ureter. Wnt ligands are released from the epithelium and act on the adjacent mesenchyme to induce smooth muscle cell (SMC) differentiation. However, through which downstream mediators it exerts these functions remains elusive. This study dissects the function of Tbx2 and Tbx3 in the ureteric mesenchyme. Tbx2 and Tbx3 are two closely related members of the T-box gene family and they act as transcriptional repressors. By using loss-of-function and gain-of-function approaches, we characterize the functions of Tbx2 and Tbx3 in the mesenchyme. We show that they mediate part of cellular functions of the Wnt signaling in the mesenchyme of the ureter. Tbx2 and Tbx3 act redundantly to induce SMC differentiation in the inner mesenchyme of the ureter as shown by the loss of SMC upon their loss in this domain. They exhibit an indirect positive regulation of Foxf1, an effector gene of sonic hedgehog signaling that induces SMC differentiation. Furthermore, they regulate Bmp4 signaling that is also required for SMC program in the ureteric mesenchyme. Tbx2 and Tbx3 are involved in the repression of fibroblast formation as demonstrated by the expansion of fibroblast markers in the inner mesenchyme of the loss-of-function mutant ureter. This finding is confirmed by the analysis of gain-of-function mutants as shown by the suppression of these markers in the outer domain of the mesenchyme upon the misexpression of TBX2 in this domain. Tbx2 and Tbx3 repress the expression of Cxcl12 and Bmper, two factors that mark the entire undifferentiated mesenchyme at early stages. Similarly, these markers are downregulated when Wnt signaling activity is ablated in the mesenchyme, pointing to defects in the patterning process in this domain. This suggests that Tbx2 and Tbx3 are involved in the patterning of the uncommitted mesenchymal precursors. These findings suggest that Tbx2 and Tbx3 are possible downstream mediators of Wnt signaling to direct patterning of uncommitted mesenchymal cells, to promote SMC program and to suppress the fibroblast formation in the inner mesenchyme of the ureter.
Benzer Tezler
- Quantitative analysis of relationships between fluxome and metabolome in Escherichia coli
Başlık çevirisi yok
HİLAL TAYMAZ NİKEREL
Doktora
İngilizce
2010
BiyoteknolojiTechnische Universiteit Delft (Delft University of Technology)PROF. DR. J. J. HEIJNEN
DR. W. M. VAN GULIK
- Astım hastalarında genetik yatkınlık, duyarlılık ve oksidatif stres göstergelerinin moleküler analizi
Molecular analysis of genetic susceptibility, sensitivity and oxidative stress markers in asthma patients
BEHNAZ KARADOĞAN
Doktora
Türkçe
2020
Allerji ve İmmünolojiİstanbul ÜniversitesiMoleküler Biyoloji ve Genetik Ana Bilim Dalı
PROF. DR. EMİNE ŞEKÜRE NAZLI ARDA
PROF. DR. ASLI GELİNCİK
- İnsan bax geni promotör bölgesinin fonksiyonel analizi
Functional analysis of human bax gen promoter region
EMİNE TORAMAN
Yüksek Lisans
Türkçe
2017
GenetikAtatürk ÜniversitesiMoleküler Biyoloji ve Genetik Ana Bilim Dalı
PROF. DR. ORHAN ERDOĞAN
- Metastatik ve nonmetastatik meme karsinomlarında hücre siklus proteinlerinin (YB-1 ve CDC6) ekspresyonu
Investigation of cell cycle protein (YB1 and CDC6) expression in metastatic and nonmetastatic breast carcinomas
MARİNA ÇEKİRDEK
- Moleculer analysis of a unique type of S(alfa)-thallassemia
Yeni bir S(alfa)-talasemi çeşidinin moleküler analizi
GÜNAY BALTA
Doktora
İngilizce
1994
BiyolojiOrta Doğu Teknik ÜniversitesiBiyoloji Ana Bilim Dalı
DOÇ. DR. SEMRA KOCABIYIK