scholarly journals In vivo clonal analysis reveals spatiotemporal regulation of thalamic nucleogenesis

PLoS Biology ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. e2005211 ◽  
Author(s):  
Samuel Z. H. Wong ◽  
Earl Parker Scott ◽  
Wenhui Mu ◽  
Xize Guo ◽  
Ella Borgenheimer ◽  
...  
Keyword(s):  
Clonal Analysis ◽  
Spatiotemporal Regulation

scholarly journals In vivo clonal analysis reveals spatiotemporal regulation of thalamic nucleogenesis

2017 ◽  
Author(s):  
Samuel Z.H. Wong ◽  
Earl Parker Scott ◽  
Wenhui Mu ◽  
Xize Guo ◽  
Ella Borgenheimer ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Clonal Analysis ◽  
Cellular Heterogeneity ◽  
Thalamic Nuclei ◽  
Fate Specification ◽  
Cell Divisions ◽  
Spatiotemporal Regulation ◽  
Short Period ◽  
Organizational Principle

ABSTRACTThe thalamus, a crucial regulator of cortical functions, is composed of many nuclei arranged in a spatially complex pattern. Thalamic neurogenesis occurs over a short period during mammalian embryonic development. These features have hampered the effort to understand how regionalization, cell divisions and fate specification are coordinated and produce a wide array of nuclei that exhibit distinct patterns of gene expression and functions. Here, we performed in vivo clonal analysis to track the divisions of individual progenitor cells and spatial allocation of their progeny in the developing mouse thalamus. Quantitative analysis of clone compositions revealed evidence for sequential generation of distinct sets of thalamic nuclei based on the location of the founder progenitor cells. Furthermore, we identified intermediate progenitor cells that produced neurons populating more than one thalamic nuclei, indicating a prolonged specification of nuclear fate. Our study reveals an organizational principle that governs the spatial and temporal progression of cell divisions and fate specification, and provides a framework for studying cellular heterogeneity and connectivity in the mammalian thalamus.

scholarly journals Illumination of neural development by in vivo clonal analysis

2018 ◽  
Vol 7 (2) ◽  
pp. 33-39 ◽  
Author(s):  
Mingrui Xu ◽  
Jingjing Wang ◽  
Xize Guo ◽  
Tingting Li ◽  
Xia Kuang ◽  
...  
Keyword(s):  
Neural Development ◽  
Clonal Analysis

scholarly journals Spatiotemporal regulation of endogenous MSCs using a functional injectable hydrogel system for cartilage regeneration

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yunsheng Dong ◽  
Yufei Liu ◽  
Yuehua Chen ◽  
Xun Sun ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
In Vivo Experiments ◽  
Spatiotemporal Regulation ◽  
Stromal Cell Derived Factor ◽  
Hydrogel System

AbstractHydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE.

scholarly journals Single cell dynamics of embryonic muscle progenitor cells in zebrafish

2018 ◽  
Author(s):  
Priyanka Sharma ◽  
Tyler D. Ruel ◽  
Katrinka M. Kocha ◽  
Shan Liao ◽  
Peng Huang
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Muscle Injury ◽  
Muscle Growth ◽  
Clonal Analysis ◽  
Muscle Stem Cells ◽  
Injury Repair ◽  
Embryonic Muscle ◽  
Muscle Progenitor Cells

ABSTRACTMuscle stem cells hold a great therapeutic potential in regenerating damaged muscles. However, the in vivo behavior of muscle stem cells during muscle growth and regeneration is still poorly understood. Using zebrafish as a model, we describe the in vivo dynamics and function of dermomyotome cells, a population of embryonic muscle progenitor cells. Dermomyotome cells are located in a superficial layer external to muscle fibers and express many extracellular matrix (ECM) genes including col1a2. Utilizing a new col1a2 transgenic line, we show that dermomyotome cells display a ramified morphology with dynamic cellular processes. Cell lineage tracing demonstrates that col1a2+ dermomyotome cells contribute to normal muscle growth as well as muscle injury repair. Combination of live imaging and single cell clonal analysis reveals a highly-choreographed process of muscle regeneration. Activated dermomyotome cells change from the quiescent ramified morphology to a polarized and elongated morphology and generate daughter cells that fuse with existing muscle fibers. Ablation of the dermomyotome severely compromises muscle injury repair. Our work provides a dynamic view of embryonic muscle progenitor cells during zebrafish muscle regeneration.Summary statementLive imaging and single cell clonal analysis reveal dynamic behaviors of zebrafish embryonic muscle progenitor cells in quiescence and activation.

scholarly journals Identification of regulatory elements required for Stra8 expression, in fetal ovarian germ cells of the mouse

Development ◽  
2021 ◽  
pp. dev.194977
Author(s):  
Chun-Wei Feng ◽  
Guillaume Burnet ◽  
Cassy M. Spiller ◽  
Fiona Ka Man Cheung ◽  
Kallayanee Chawengsaksophak ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Germ Cells ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Egfp Expression ◽  
Spatiotemporal Regulation ◽  
Targeted Mutation ◽  
Fetal Ovary

In mice, the entry of germ cells into meiosis critically depends on the expression of stimulated by retinoic acid gene 8 (Stra8). Stra8 is expressed specifically in pre-meiotic germ cells of females and males, at fetal and postnatal stages respectively, but the mechanistic details of its spatiotemporal regulation are yet to be defined. In particular, there has been considerable debate regarding whether retinoic acid is required, in vivo, to initiate Stra8 expression in the mouse fetal ovary. We show that the distinctive anterior-to-posterior pattern of Stra8 initiation, characteristic of germ cells in the fetal ovary, is faithfully recapitulated when 2.9 kb of the Stra8 promoter is used to drive eGFP expression. Using in vitro transfection assays of cut-down and mutant constructs we identified two functional retinoic acid responsive elements (RAREs) within this 2.9 kb regulatory element. We also show that the transcription factor DMRT1 enhances Stra8 expression, but only in the presence of RA and the most proximal RARE. Finally, we used CRISPR/Cas9-mediated targeted mutation studies to demonstrate that both RAREs are required for optimal Stra8 expression levels, in vivo.

scholarly journals Ret Signaling Is Required for Tooth Pulp Innervation during Organogenesis

2019 ◽  
Vol 98 (6) ◽  
pp. 705-712 ◽  
Author(s):  
C.R. Donnelly ◽  
A.A. Shah ◽  
E.B. Suh ◽  
B.A. Pierchala
Keyword(s):  
Dental Pulp ◽  
Substantial Reduction ◽  
Cell Types ◽  
Conditional Knockout ◽  
Tooth Pulp ◽  
Spatiotemporal Regulation ◽  
Basic Biology ◽  
And Function ◽  
Tooth Innervation

During organogenesis, the timing and patterning of dental pulp innervation require both chemoattractive and chemorepellent cues for precise spatiotemporal regulation. Our understanding of the signaling mechanisms that regulate tooth innervation during development, as well as the basic biology of these sensory neurons, remains rudimentary. In this study, we analyzed the expression and function of glial cell line–derived neurotrophic factor (GDNF) and its receptor tyrosine kinase, Ret, in the regulation of innervation of the mouse tooth pulp by dental pulpal afferent (DPA) neurons of the trigeminal ganglion (TG). Using reporter mouse models, we demonstrate that Ret is highly expressed by a subpopulation of DPA neurons projecting to the tooth pulp at both postnatal day 7 (P7) and in the adult. In the adult tooth, GDNF is highly expressed by many cell types throughout the dental pulp. Using a ubiquitous tamoxifen (TMX)–inducible Cre ( UBC-Cre/ERT2) line crossed to Ret conditional knockout mice ( Retfx/fx), Ret was deleted immediately prior to tooth innervation, and the neural projections into P7 molars were analyzed. TMX treatment was efficient in ablating >95% of Ret protein. We observed that UBC-Cre/ERT2; Retfx/fx mice had a significant reduction in the total number of neurites present within the pulp at P7, with a significant accumulation of aberrant fibers in the dental follicle and periodontium. In agreement with these findings, inhibition of Ret signaling through in vivo administration of a highly specific pharmacologic inhibitor (1NM-PP1) of Ret also caused a substantial reduction in pulpal innervation. Taken together, these findings indicate that Ret signaling regulates the timing and patterning of tooth innervation by dental primary afferent neurons of the TG during organogenesis and provide a rationale to explore whether alterations in the GDNF-Ret pathway contribute to pathophysiological conditions in the adult dentition.

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