Spatial and temporal expression patterns of Atoh1 during mice cerebellar development

XUE Sai-Sai; CHEN Li-Ping; LI Ying; WU Yan; WU Hai-Tao

doi:10.16098/j.issn.0529-1356.2023.02.002

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Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (2) : 134-141. DOI: 10.16098/j.issn.0529-1356.2023.02.002

Neurobiology

Spatial and temporal expression patterns of Atoh1 during mice cerebellar development

XUE Sai-sai¹ CHEN Li-ping² LI Ying³ WU Yan² WU Hai-tao^1,2*

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Abstract

Objective To investigated the spatial and temporal expression of Atoh1 mRNA and protein level during the cerebellar development. Methods The frozen cerebellum sections of mice at different developmental stages were used to analyze the temporal and spatial expression patterns of Atoh1 mRNA by RNA scope technique, n=3 for each group. Meanwhile, two reporter mice with different genetic modification method were utilized to analyze the spatialand temporal expression of Atoh1 at the protein level by immunofluorescence staining, n=3 for each group. Results Atoh1 mRNA was highly expressed in the embryonic cerebellar rhombic lip (RL) and the external granule layer (EGL). At the protein level, staining result of Atoh1-3*V5-P2A-tdTomato/+ knockin mice showed that Atoh1 was mainly expressed in the RL and the outer layer of the proliferative EGL. Atoh1-Cre;tdTomato/+ transgenic reporter mice showed that tdTomato positive cells were highly expressed in the EGL and the inner granule cell layer (IGL) during the whole granule cells development. Conclusion During cerebellar development, Atoh1 mRNA and protein were highly expressed in the embryonic rhombic lip and postnatal external granule layer. However, at the protein level, the expression of Atoh1 in the rhombic lip and external granule layer were different between knockin mice and transgenic mice.

Key words

Cerebellum / Development / Atoh1 / Granule neuron precursor cell / RNA scope / Mouse

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XUE Sai-sai CHEN Li-ping LI Ying WU Yan WU Hai-tao. Spatial and temporal expression patterns of Atoh1 during mice cerebellar development[J]. Acta Anatomica Sinica. 2023, 54(2): 134-141 https://doi.org/10.16098/j.issn.0529-1356.2023.02.002

References

［1］Sgaier SK, Millet S, Villanueva MP, et al. Morphogenetic and cellular movements that shape the mouse cerebellum; insights from genetic fate mapping ［J］. Neuron, 2005, 45(1): 27-40.

［2］Voogd J, Glickstein M. The anatomy of the cerebellum ［J］. Trends Cogn Sci, 1998, 2(9): 307-313.

［3］Butts T, Green MJ, Wingate RJ. Development of the cerebellum: simple steps to make a 'little brain' ［J］. Development, 2014, 141(21): 4031-4041.

［4］Millen KJ, Steshina EY, Iskusnykh IY, et al. Transformation of the cerebellum into more ventral brainstem fates causes cerebellar agenesis in the absence of Ptf1a function ［J］. Proc Natl Acad Sci USA, 2014, 111(17): E1777-1786.

［5］Wang VY, Zoghbi HY. Genetic regulation of cerebellar development ［J］. Nat Rev Neurosci, 2001, 2(7): 484-491.

［6］Komuro H, Yacubova E. Recent advances in cerebellar granule cell migration ［J］. Cell Mol Life Sci, 2003, 60(6): 1084-1098.

［7］Yan MCh，Niu YL，Wang XQ，et al. Reelin and the cerebellar development——the regulatory effect of Notch1 signaling pathways［J］．Acta Anatomica Sinica，2015，46(2) : 182-189．(in Chinese)

鄢明超牛艳丽, 王小青，等. Reelin与小脑发育——Notch1 信号通路的调节作用［J］. 解剖学报, 2015, 46(2): 182-189.

［8］Yang H, Xie X, Deng M, et al. Generation and characterization of Atoh1-Cre knock-in mouse line ［J］. Genesis, 2010, 48(6): 407-413.

［9］Chang CH, Zanini M, Shirvani H, et al. Atoh1 controls primary cilia formation to allow for SHH-triggered granule neuron progenitor proliferation ［J］. Dev Cell, 2019, 48(2): 184-199.

［10］Ben-Arie N, Bellen HJ, Armstrong DL, et al. Math1 is essential for genesis of cerebellar granule neurons ［J］. Nature, 1997, 390(6656): 169-172.

［11］Akazawa C, Ishibashi M, Shimizu C, et al. A mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal is a positive transcriptional regulator expressed in the developing nervous system ［J］. J Biol Chem, 1995, 270(15): 8730-8738.

［12］Luo Z, Du Y, Li S, et al. Three distinct Atoh1 enhancers cooperate for sound receptor hair cell development ［J］. Proc Natl Acad Sci USA, 2022, 119(32): e2119850119.

［13］Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum ［J］. Cell Rep, 2021, 35(10): 109208.

［14］Castellino RC, Kenney AM. Atoh1/MATH1 adds up to ciliogenesis for transducing SHH signaling in the cerebellum ［J］. Dev Cell, 2019, 48(2): 129-130.

［15］Yeung J, Ha TJ, Swanson DJ, et al. A novel and multivalent role of Pax6 in cerebellar development ［J］. J Neurosci, 2016, 36(35): 9057-9069.

［16］Carter RA, Bihannic L, Rosencrance C, et al. A Single-cell transcriptional atlas of the developing murine cerebellum ［J］. Curr Biol, 2018, 28(18):2910-2920.

［17］Choi Y, Borghesani PR, Chan JA, et al. Migration from a mitogenic niche promotes cell-cycle exit ［J］. J Neurosci, 2005, 25(45): 10437-10445.

［18］Consalez GG, Goldowitz D, Casoni F, et al. Origins, development, and compartmentation of the granule cells of the cerebellum ［J］. Front Neural Circuits, 2020, 14: 611841.

［19］Khouri-Farah N, Guo Q, Morgan K, et al. Integrated single-cell transcriptomic and epigenetic study of cell state transition and lineage commitment in embryonic mouse cerebellum ［J］. Sci Adv, 2022, 8(13): eabl9156.

［20］Wagner MJ, Kim TH, Savall J, et al. Cerebellar granule cells encode the expectation of reward ［J］. Nature, 2017, 544(7648): 96-100.

［21］van der Heijden ME, Sillitoe RV. Interactions between purkinje cells and granule cells coordinate the development of functional cerebellar circuits ［J］. Neuroscience, 2021, 462: 4-21.

［22］Bengtsson F, J?rntell H. Sensory transmission in cerebellar granule cells relies on similarly coded mossy fiber inputs ［J］. Proc Natl Acad Sci USA, 2009, 106(7): 2389-2394.

［23］Becker MI, Person AL. Cerebellar granule cells expand their talents ［J］. Nat Neurosci, 2017, 20(5): 633-634.

［24］Giovannucci A, Badura A, Deverett B, et al. Cerebellar granule cells acquire a widespread predictive feedback signal during motor learning ［J］. Nat Neurosci, 2017, 20(5): 727-734.