Myh6-Cre transgenic mouse line was known to express Cre recombinase only in the heart. Nevertheless, during breeding Myh6-Cre to Rosa26fstdTom reporter (tdTom) mouse line, we observed that a significant part of their F2 tdTom/+ offspring had tdTom reporter gene universally activated. Our results show that Myh6-Cre transgenic mice have Cre recombinase activity in a subpopulation of the male germline cells, and that Myh6 gene transcripts are enriched in the interstitial Leydig cells and the undifferentiated spermatogonia stem cells. In summary, the current study confirms that the previously known "heart-specific" Myh6 promoter drives Cre expression in the testis.

• MeSH
• integrasy * genetika   metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• promotorové oblasti (genetika) genetika   MeSH
• zárodečné buňky * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts.

• MeSH
• chondrocyty cytologie   účinky léků   metabolismus   MeSH
• čichová sliznice cytologie   účinky léků   růst a vývoj   metabolismus   MeSH
• embryo savčí MeSH
• homeodoménové proteiny genetika   metabolismus   MeSH
• integrasy genetika   metabolismus   MeSH
• kolagen typ II genetika   metabolismus   MeSH
• lidé MeSH
• maxilofaciální vývoj genetika   MeSH
• morfogeneze účinky léků   genetika   MeSH
• mozek účinky léků   růst a vývoj   metabolismus   MeSH
• mutageny aplikace a dávkování   MeSH
• myši transgenní MeSH
• myši MeSH
• nosní chrupavky cytologie   účinky léků   růst a vývoj   metabolismus   MeSH
• obličej anatomie a histologie   embryologie   MeSH
• obličejové kosti cytologie   účinky léků   růst a vývoj   metabolismus   MeSH
• proteiny hedgehog genetika   metabolismus   MeSH
• rekombinantní fúzní proteiny genetika   metabolismus   MeSH
• signální transdukce * MeSH
• tamoxifen aplikace a dávkování   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cell reprogramming requires efficient delivery of reprogramming transcription factors into the cell nucleus. Here, we compared the robustness and workload of two protein delivery methods that avoid the risk of genomic integration. The first method is based on fusion of the protein of interest to a protein transduction domain (PTD) for delivery across the membranes of target cells. The second method relies on de novo synthesis of the protein of interest inside the target cells utilizing synthetic mRNA (syn-mRNA) as a template. We established a Cre/lox reporter system in three different cell types derived from human (PANC-1, HEK293) and rat (BRIN-BD11) tissues and used Cre recombinase to model a protein of interest. The system allowed constitutive expression of red fluorescence protein (RFP), while green fluorescence protein (GFP) was expressed only after the genomic action of Cre recombinase. The efficiency of protein delivery into cell nuclei was quantified as the frequency of GFP+ cells in the total cell number. The PTD method showed good efficiency only in BRIN-BD11 cells (68%), whereas it failed in PANC-1 and HEK293 cells. By contrast, the syn-mRNA method was highly effective in all three cell types (29-71%). We conclude that using synthetic mRNA is a more robust and less labor-intensive approach than using the PTD-fusion alternative.

• MeSH
• buněčné jádro metabolismus   MeSH
• buněčné klony MeSH
• DNA metabolismus   MeSH
• genetické inženýrství MeSH
• HEK293 buňky MeSH
• integrasy metabolismus   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• proteinové domény MeSH
• průtoková cytometrie MeSH
• rekombinantní fúzní proteiny chemie   metabolismus   MeSH
• reprodukovatelnost výsledků MeSH
• technika přenosu genů * MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The neural crest (NC) is crucial for the evolutionary diversification of vertebrates. NC cells are induced at the neural plate border by the coordinated action of several signaling pathways, including Wnt/β-catenin. NC cells are normally generated in the posterior neural plate border, whereas the anterior neural fold is devoid of NC cells. Using the mouse model, we show here that active repression of Wnt/β-catenin signaling is required for maintenance of neuroepithelial identity in the anterior neural fold and for inhibition of NC induction. Conditional inactivation of Tcf7l1, a transcriptional repressor of Wnt target genes, leads to aberrant activation of Wnt/β-catenin signaling in the anterior neuroectoderm and its conversion into NC. This reduces the developing prosencephalon without affecting the anterior-posterior neural character. Thus, Tcf7l1 defines the border between the NC and the prospective forebrain via restriction of the Wnt/β-catenin signaling gradient.

• MeSH
• beta-katenin metabolismus   MeSH
• biologické markery metabolismus   MeSH
• buněčný rodokmen * MeSH
• crista neuralis cytologie   metabolismus   MeSH
• dánio pruhované metabolismus   MeSH
• defekty neurální trubice metabolismus   patologie   MeSH
• delece genu MeSH
• fenotyp MeSH
• integrasy metabolismus   MeSH
• lidé MeSH
• myši transgenní MeSH
• přední mozek embryologie   metabolismus   MeSH
• protein 1 podobný transkripčnímu faktoru 7 metabolismus   MeSH
• proteiny dánia pruhovaného metabolismus   MeSH
• represorové proteiny metabolismus   MeSH
• signální dráha Wnt MeSH
• transdiferenciace buněk MeSH
• transkripční faktor AP-2 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

For all sensory organs, the establishment of spatial and temporal cortical resolution is assumed to be initiated by the first sensory experience and a BDNF-dependent increase in intracortical inhibition. To address the potential of cortical BDNF for sound processing, we used mice with a conditional deletion of BDNF in which Cre expression was under the control of the Pax2 or TrkC promoter. BDNF deletion profiles between these mice differ in the organ of Corti (BDNF (Pax2) -KO) versus the auditory cortex and hippocampus (BDNF (TrkC) -KO). We demonstrate that BDNF (Pax2) -KO but not BDNF (TrkC) -KO mice exhibit reduced sound-evoked suprathreshold ABR waves at the level of the auditory nerve (wave I) and inferior colliculus (IC) (wave IV), indicating that BDNF in lower brain regions but not in the auditory cortex improves sound sensitivity during hearing onset. Extracellular recording of IC neurons of BDNF (Pax2) mutant mice revealed that the reduced sensitivity of auditory fibers in these mice went hand in hand with elevated thresholds, reduced dynamic range, prolonged latency, and increased inhibitory strength in IC neurons. Reduced parvalbumin-positive contacts were found in the ascending auditory circuit, including the auditory cortex and hippocampus of BDNF (Pax2) -KO, but not of BDNF (TrkC) -KO mice. Also, BDNF (Pax2) -WT but not BDNF (Pax2) -KO mice did lose basal inhibitory strength in IC neurons after acoustic trauma. These findings suggest that BDNF in the lower parts of the auditory system drives auditory fidelity along the entire ascending pathway up to the cortex by increasing inhibitory strength in behaviorally relevant frequency regions. Fidelity and inhibitory strength can be lost following auditory nerve injury leading to diminished sensory outcome and increased central noise.

• MeSH
• colliculus inferior patologie   patofyziologie   MeSH
• delece genu MeSH
• hluk * MeSH
• integrasy metabolismus   MeSH
• kochlea metabolismus   MeSH
• mozkový neurotrofický faktor metabolismus   MeSH
• myši knockoutované MeSH
• promotorové oblasti (genetika) genetika   MeSH
• receptor trkC metabolismus   MeSH
• rizikové faktory MeSH
• sluch MeSH
• sluchové kmenové evokované potenciály MeSH
• sluchové korové centrum metabolismus   patologie   patofyziologie   MeSH
• sluchový práh MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

During mouse eye development, all retinal cell types are generated from the population of retina-committed progenitors originating from the neuroepithelium of the optic vesicle. Conditional gene inactivation provides an efficient tool for studying the genetic basis of the developing retina; however, the number of retina-specific Cre lines is limited. Here we report generation of the mRx-Cre BAC transgenic mouse line in which the expression of Cre recombinase is controlled by regulatory sequences of the mouse Rx gene, one of the earliest determinants of retinal development. When mRx-Cre transgenic mice were crossbred with the ROSA26R or ROSA26R-EYFP reporter lines, the Cre activity was observed in the optic sulcus from embryonic day 8.5 onwards and later in all progenitors residing in the neuroepithelium of the optic cup. Our results suggest that mRx-Cre provides a unique tool for functional genetic studies in very early stages of retinal development. Moreover, since eye organogenesis is dependent on the inductive signals between the optic vesicle and head surface ectoderm, the inductive ability of the optic vesicle can be analyzed using mRx-Cre transgenic mice.

• MeSH
• časové faktory MeSH
• delece genu * MeSH
• genetické inženýrství metody   MeSH
• homeodoménové proteiny genetika   MeSH
• integrasy metabolismus   MeSH
• kmenové buňky cytologie   metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• oční proteiny genetika   MeSH
• rekombinace genetická MeSH
• retina cytologie   MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene located on chromosome 17p13.3, a region frequently hypermethylated or deleted in human neoplasias. In mouse, Hic1 is essential for embryonic development and exerts an antitumor role in adult animals. Since Hic1-deficient mice die perinatally, we generated a conditional Hic1 null allele by flanking the Hic1-coding region by loxP sites. When crossed to animals expressing Cre recombinase in a cell-specific manner, the Hic1 conditional mice will provide new insights into the function of Hic1 in developing and mature tissues. Additionally, we used gene targeting to replace sequence-encoding amino acids 186-893 of Hic1 by citrine fluorescent protein cDNA. We demonstrate that the distribution of Hic1-citrine fusion polypeptide corresponds to the expression pattern of wild-type Hic1. Consequently, Hic1-citrine "reporter" mice can be used to monitor the activity of the Hic1 locus using citrine fluorescence.

• MeSH
• alely MeSH
• delece genu MeSH
• DNA vazebné proteiny genetika   MeSH
• embryo savčí metabolismus   MeSH
• genový targeting MeSH
• integrasy genetika   metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• reportérové geny MeSH
• transkripční faktory Krüppel-like genetika   MeSH
• transkripční faktory genetika   MeSH
• tumor supresorové geny MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH