Yap/Taz are required for establishing the cerebellar radial glia scaffold and proper foliation

被引:9
作者
Hughes, Lucinda J. [1 ,2 ]
Park, Raehee [1 ]
Lee, Min Jung [1 ]
Terry, Bethany K. [1 ,2 ]
Lee, David J. [1 ]
Kim, Hansol [1 ]
Cho, Seo-Hee [1 ]
Kim, Seonhee [1 ]
机构
[1] Temple Univ, Lewis Katz Sch Med, Dept Anat & Cell Biol, Shriners Hosp Pediat Res Ctr, 3500 North Broad St, Philadelphia, PA 19140 USA
[2] Temple Univ, Grad Program Biomed Sci, Lewis Katz Sch Med, Philadelphia, PA 19140 USA
基金
美国国家卫生研究院;
关键词
HIPPO-YAP PATHWAY; PROGENITOR CELLS; BERGMANN GLIA; MEDULLOBLASTOMA; REGENERATION; FATE; TAZ; DOWNSTREAM; GENERATION; EXPRESSION;
D O I
10.1016/j.ydbio.2019.10.002
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Yap/Taz are well-established downstream effectors of the Hippo pathway, known to regulate organ size by directing proliferation and apoptosis. Although the functions of Yap/Taz have been extensively studied, little is known about their role in brain development. Here, through genetic ablation, we show that Yap/Taz are required for cerebellar morphogenesis. Yap/Taz deletion in neural progenitors causes defects in secondary fissure formation, leading to abnormal folia development. Although they seemed very likely to serve an important function in the development of cerebellar granule cell precursors, Yap/Taz are dispensable for their proliferation. Furthermore, Yap/Taz loss does not rescue the medulloblastoma phenotype caused by constitutively active Smoothened. Importantly, Yap/Taz are highly expressed in radial glia and play a crucial role in establishing the radial scaffold and cellular polarity of neural progenitors during embryogenesis. We found that Yap/Taz are necessary to establish and maintain junctional integrity of cerebellar neuroepithelium as prominent junction proteins are not maintained at the apical junction in the absence of Yap/Taz. Our study identifies a novel function of Yap/Taz in cerebellar foliation and finds that they are required to establish the radial glia scaffold and junctional stability.
引用
收藏
页码:150 / 162
页数:13
相关论文
共 63 条
[1]   Origin, lineage and function of cerebellar glia [J].
Buffo, Annalisa ;
Rossi, Ferdinando .
PROGRESS IN NEUROBIOLOGY, 2013, 109 :42-63
[2]   Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts [J].
Calvo, Fernando ;
Ege, Nil ;
Grande-Garcia, Araceli ;
Hooper, Steven ;
Jenkins, Robert P. ;
Chaudhry, Shahid I. ;
Harrington, Kevin ;
Williamson, Peter ;
Moeendarbary, Emad ;
Charras, Guillaume ;
Sahai, Erik .
NATURE CELL BIOLOGY, 2013, 15 (06) :637-+
[3]   Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development [J].
Cappello, Silvia ;
Gray, Mary J. ;
Badouel, Caroline ;
Lange, Simona ;
Einsiedler, Melanie ;
Srour, Myriam ;
Chitayat, David ;
Hamdan, Fadi F. ;
Jenkins, Zandra A. ;
Morgan, Tim ;
Preitner, Nadia ;
Uster, Tami ;
Thomas, Jackie ;
Shannon, Patrick ;
Morrison, Victoria ;
Di Donato, Nataliya ;
Van Maldergem, Lionel ;
Neuhann, Teresa ;
Newbury-Ecob, Ruth ;
Swinkells, Marielle ;
Terhal, Paulien ;
Wilson, Louise C. ;
Zwijnenburg, Petra J. G. ;
Sutherland-Smith, Andrew J. ;
Black, Michael A. ;
Markie, David ;
Michaud, Jacques L. ;
Simpson, Michael A. ;
Mansour, Sahar ;
McNeill, Helen ;
Goetz, Magdalena ;
Robertson, Stephen P. .
NATURE GENETICS, 2013, 45 (11) :1300-+
[4]   Genetic ablation of Pals1 in retinal progenitor cells models the retinal pathology of Leber congenital amaurosis [J].
Cho, Seo-Hee ;
Kim, Jin Young ;
Simons, David L. ;
Song, Ji Yun ;
Le, Julie H. ;
Swindell, Eric C. ;
Jamrich, Milan ;
Wu, Samuel M. ;
Kim, Seonhee .
HUMAN MOLECULAR GENETICS, 2012, 21 (12) :2663-2676
[5]   YB-1 is elevated in medulloblastoma and drives proliferation in Sonic hedgehog-dependent cerebellar granule neuron progenitor cells and medulloblastoma cells [J].
Dey, A. ;
Robitaille, M. ;
Remke, M. ;
Maier, C. ;
Malhotra, A. ;
Gregorieff, A. ;
Wrana, J. L. ;
Taylor, M. D. ;
Angers, S. ;
Kenney, A. M. .
ONCOGENE, 2016, 35 (32) :4256-4268
[6]   Nestin-Cre transgenic mouse line Nes-Cre1 mediates highly efficient Cre/IoxP mediated recombination in the nervous system, kidney, and somite-derived tissues [J].
Dubois, Nicole C. ;
Hofmann, Denise ;
Kaloulis, Kostas ;
Bishop, J. M. ;
Trumpp, Andreas .
GENESIS, 2006, 44 (08) :355-360
[7]   Oncogenic YAP promotes radioresistance and genomic instability in medulloblastoma through IGF2-mediated Akt activation [J].
Fernandez-L, A. ;
Squatrito, M. ;
Northcott, P. ;
Awan, A. ;
Holland, E. C. ;
Taylor, M. D. ;
Nahle, Z. ;
Kenney, A. M. .
ONCOGENE, 2012, 31 (15) :1923-1937
[8]   YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation [J].
Fernandez-L, Africa ;
Northcott, Paul A. ;
Dalton, James ;
Fraga, Charles ;
Ellison, David ;
Angers, Stephane ;
Taylor, Michael D. ;
Kenney, Anna Marie .
GENES & DEVELOPMENT, 2009, 23 (23) :2729-2741
[9]   Pten Deletion in Adult Neural Stem/Progenitor Cells Enhances Constitutive Neurogenesis [J].
Gregorian, Caroline ;
Nakashima, Jonathan ;
Le Belle, Janel ;
Ohab, John ;
Kim, Rachel ;
Liu, Annie ;
Smith, Kate Barzan ;
Groszer, Matthias ;
Garcia, A. Denise ;
Sofroniew, Michael V. ;
Carmichael, Thomas ;
Kornblum, Harley I. ;
Liu, Xin ;
Wu, Hong .
JOURNAL OF NEUROSCIENCE, 2009, 29 (06) :1874-1886
[10]   Yap-dependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer [J].
Gregorieff, Alex ;
Liu, Yu ;
Inanlou, Mohammad R. ;
Khomchuk, Yuliya ;
Wrana, Jeffrey L. .
NATURE, 2015, 526 (7575) :715-718