The different modes of stem cell division are tightly regulated to balance growth and differentiation during organ development and homeostasis, and these regulatory processes are subverted in tumor formation. Here, we developed markers that provided the single-cell resolution necessary to quantify the three modes of division taking place in the developing nervous system in vivo: self-expanding, PP; self-replacing, PN; and self-consuming, NN. Using these markers and a mathematical model that predicts the dynamics of motor neuron progenitor division, we identify a role for the morphogen Sonic hedgehog in the maintenance of stem cell identity in the developing spinal cord. Moreover, our study provides insight into the process linking lineage commitment to neurogenesis with changes in cell-cycle parameters. As a result, we propose a challenging model in which the external Sonic hedgehog signal dictates stem cell identity, reflected in the consequent readjustment of cell-cycle parameters.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.celrep.2013.06.038 | DOI Listing |
Congenit Anom (Kyoto)
December 2024
Department of Molecular Craniofacial Embryology and Oral Histology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Sonic hedgehog (Shh) is expressed in the oropharyngeal epithelium, including the frontonasal ectodermal zone (FEZ), which is defined as the boundary between Shh and Fgf8 expression domains in the frontonasal epithelium. To investigate the role of SHH signaling from the oropharyngeal epithelium, we generated mice in which Shh expression is specifically deleted in the oropharyngeal epithelium (Isl1-Cre; Shh). In the mutant mouse, Shh expression was excised in the oropharyngeal epithelium as well as FEZ and ventral forebrain, consistent with the expression pattern of Isl1.
View Article and Find Full Text PDFFront Neurosci
December 2024
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Background: Extracellular vesicles are easily accessible in various biofluids and allow the assessment of disease-related changes in the proteome. This has made them a promising target for biomarker studies, especially in the field of neurodegeneration where access to diseased tissue is very limited. Genetic variants in the LRRK2 gene have been linked to both familial and sporadic forms of Parkinson's disease.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
There is an urgent necessity to devise efficient tactics to tackle the inevitable development of resistance to osimertinib, which is a third-generation epidermal growth factor receptor (EGFR) inhibitor used in treating EGFR-mutant nonsmall cell lung cancer (NSCLC). This study demonstrates that combining itraconazole with osimertinib synergistically reduces the proliferation and migration, enhances the apoptosis of osimertinib-resistant cells, and effectively inhibits the growth of osimertinib-resistant tumors. Mechanistically, itraconazole combined with osimertinib promotes the proteasomal degradation of sonic hedgehog (SHH), resulting in inactivation of the SHH/Dual-specificity phosphatase 13B (DUSP13B)/p-STAT3 and Hedgehog pathways, suppressing Myc proto-oncogene protein (c-Myc).
View Article and Find Full Text PDFAm J Physiol Cell Physiol
December 2024
Institute of Physiology, University Duisburg-Essen, Essen, Germany.
Over the last few decades, the primary cilium, an inconspicuous cell organelle, has increasingly become the focus of current research. The primary cilium is a microtubule-based, non-motile, antenna-like structure that is present on almost all mammalian cells. The ciliary membrane incorporates a large number of receptor molecules, which further characterize this cellular organelle.
View Article and Find Full Text PDFJ Oral Biosci
December 2024
Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan. Electronic address:
Objective: This study aimed to evaluate the role of the chromodomain helicase DNA-binding protein 3 (CHD3) in tooth morphogenesis in Chd3 knockout mice.
Methods: Chd3 knockout mice were generated using the CRISPR-Cas9 method. Mandibular first molars were extracted from the mice and their littermates and morphometrically analyzed.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!