| Author |
Park, Jun Young Hughes, Lucinda J. Moon, Uk Yeol Park, Raehee Kim, Sang-Bae Tran, Khoi Lee, Ju-Seog Cho, Seo-Hee Kim, Seonhee |
| Description |
Country affiliation: United States Author Affiliation: Park JY ( Shriners Hospitals Pediatric Research Center, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.); Hughes LJ ( Shriners Hospitals Pediatric Research Center, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA Graduate Program of Biomedical Sciences, Temple University School of Medicine, Philadelphia, PA 19140, USA.); Moon UY ( Shriners Hospitals Pediatric Research Center, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.); Park R ( Shriners Hospitals Pediatric Research Center, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.); Kim SB ( Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.); Tran K ( Shriners Hospitals Pediatric Research Center, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.); Lee JS ( Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.); Cho SH ( Shriners Hospitals Pediatric Research Center, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.); Kim S ( Shriners Hospitals Pediatric Research Center, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA seonhee.kim@temple.edu.) |
| Abstract |
Through their biased localization and function within the cell, polarity complex proteins are necessary to establish the cellular asymmetry required for tissue organization. Well-characterized germinal zones, mitogenic signals and cell types make the cerebellum an excellent model for addressing the crucial function of polarity complex proteins in the generation and organization of neural tissues. Deletion of the apical polarity complex protein Pals1 in the developing cerebellum results in a remarkably undersized cerebellum with disrupted layers in poorly formed folia and strikingly reduced granule cell production. We demonstrate that Pals1 is not only essential for cerebellum organogenesis, but also for preventing premature differentiation and thus maintaining progenitor pools in cerebellar germinal zones, including cerebellar granule neuron precursors in the external granule layer. In the Pals1 mouse mutants, the expression of genes that regulate the cell cycle was diminished, correlating with the loss of the proliferating cell population of germinal zones. Furthermore, enhanced Shh signaling through activated Smo cannot overcome impaired cerebellar cell generation, arguing for an epistatic role of Pals1 in proliferation capacity. Our study identifies Pals1 as a novel intrinsic factor that regulates the generation of cerebellar cells and Pals1 deficiency as a potential inhibitor of overactive mitogenic signaling. |
| Subject Keyword |
Discipline Developmental Discipline Biology Cell Proliferation Genetics Cerebellum Embryology Membrane Proteins Metabolism Neurogenesis Physiology Nucleoside-phosphate Kinase Stem Cells Cytology Animals Cell Cycle Gene Expression Regulation, Developmental Hedgehog Proteins Mice Mice, Knockout Neuroglia Organogenesis Receptors, G-protein-coupled Signal Transduction Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
