Sonic Hedgehog Signaling in Cerebellar Development and Cancer

Wang, Wan-Chen; Shiraishi, Ryo; Kawauchi, Daisuke

doi:10.3389/fcell.2022.864035

Cited by 19 publications

(14 citation statements)

References 172 publications

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“…From the historical controversy between the reticulon and neuron theories ( 3 , 4 ), it is plausible that synaptic transmission does not solely explain how brain cells communicate. During development, brain cells communicate to orchestrate cell divisions and migrations in the absence of synapses; this intercellular communication relies on gap junctions and mitogens ( 5 ), which contribute to the establishment of neuronal assemblies.…”

Section: Introductionmentioning

confidence: 99%

3D reconstruction of the cerebellar germinal layer reveals tunneling connections between developing granule cells

et al. 2023

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The difficulty of retrieving high-resolution, in vivo evidence of the proliferative and migratory processes occurring in neural germinal zones has limited our understanding of neurodevelopmental mechanisms. Here, we used a connectomic approach using a high-resolution, serial-sectioning scanning electron microscopy volume to investigate the laminar cytoarchitecture of the transient external granular layer (EGL) of the developing cerebellum, where granule cells coordinate a series of mitotic and migratory events. By integrating image segmentation, three-dimensional reconstruction, and deep-learning approaches, we found and characterized anatomically complex intercellular connections bridging pairs of cerebellar granule cells throughout the EGL. Connected cells were either mitotic, migratory, or transitioning between these two cell stages, displaying a chronological continuum of proliferative and migratory events never previously observed in vivo at this resolution. This unprecedented ultrastructural characterization poses intriguing hypotheses about intercellular connectivity between developing progenitors and its possible role in the development of the central nervous system.

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Section: Introductionmentioning

confidence: 99%

3D reconstruction of the cerebellar germinal layer reveals tunneling connections between developing granule cells

et al. 2023

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“…SHH signaling is involved in the dorsal-ventral axis and in mid-line formation, digit patterning, and cerebellum development in embryogenesis ( Harfe et al, 2004 ; Ribes and Briscoe, 2009 ; Wang et al, 2022 ). When the SHH ligand binds to the PTCH1 receptor, which is the 12-transmembrane patched 1 protein localized on the ciliary membrane in the absence of SHH ligand, it translocates to the outside of the cilia.…”

Section: Primary Cilia-related Signal Transduction In the Context Of ...mentioning

confidence: 99%

Cholesterol in the ciliary membrane as a therapeutic target against cancer

Kimura

Morita²,

Hosoba³

et al. 2023

Front. Mol. Biosci.

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Primary cilium is a non-motile, antenna-like structure that develops in the quiescent G0 phase-cell surface. It is composed of an array of axonemal microtubules polymerized from the centrosome/basal body. The plasma membrane surrounding the primary cilium, which is called the ciliary membrane, contains a variety of receptors and ion channels, through which the cell receives extracellular chemical and physical stimuli to initiate signal transduction. In general, primary cilia disappear when cells receive the proliferative signals to re-enter the cell cycle. Primary cilia thus cannot be identified in many malignant and proliferative tumors. In contrast, some cancers, including basal cell carcinoma, medulloblastoma, gastrointestinal stromal tumor, and other malignancies, retain their primary cilia. Importantly, it has been reported that the primary cilia-mediated oncogenic signals of Hedgehog, Wnt, and Aurora kinase A are involved in the tumorigenesis and tumor progression of basal cell carcinoma and some types of medulloblastoma. It has also been demonstrated that cholesterol is significantly more enriched in the ciliary membrane than in the rest of the plasma membrane to ensure Sonic hedgehog signaling. A series of epidemiological studies on statin drugs (cholesterol-lowering medication) demonstrated that they prevent recurrence in a wide range of cancers. Taken together, ciliary cholesterol could be a potential therapeutic target in primary cilia-dependent progressive cancers.

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“…(2022) demonstrated that Surf4 was required for sonic hedgehog (Shh) export from the ER in Hela and HEK293T cells. Shh is an important signaling molecule that plays a critical role in cell differentiation and contributes to the development and progression of numerous cancers ( Wang et al., 2022 ). Therefore, Surf4 may exert its oncogenic role by upregulating BIRC3 expression and/or promoting ER–Golgi trafficking of Shh.…”

Section: Surf4 a Highly Conserved Cargo Receptormentioning

confidence: 99%

Surf4, cargo trafficking, lipid metabolism, and therapeutic implications

Shen

Qin

et al. 2022

Journal of Molecular Cell Biology

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Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum (ER) membrane. It is ubiquitously expressed and functions as a cargo receptor, mediating cargo transport from the ER and the Golgi apparatus via the canonical coat protein complex II (COPII)-coated vesicles or specific vesicles. It also participates in ER–Golgi protein trafficking through a tubular network. Meanwhile, it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through COPI-coated vesicles. Surf4 can selectively mediate export of diverse cargos, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), very low-density lipoprotein (VLDL), progranulin, α1-antitrypsin, STING, proinsulin, and erythropoietin. It has been implicated in facilitating VLDL secretion, promoting cell proliferation and migration, and increasing replication of positive-strand RNA viruses. Therefore, Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target. However, the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER–Golgi protein trafficking remain elusive. Here, we summarize the most recent advances in Surf4, focusing on its role in lipid metabolism.

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Sonic Hedgehog Signaling in Cerebellar Development and Cancer

Cited by 19 publications

References 172 publications

3D reconstruction of the cerebellar germinal layer reveals tunneling connections between developing granule cells

3D reconstruction of the cerebellar germinal layer reveals tunneling connections between developing granule cells

Cholesterol in the ciliary membrane as a therapeutic target against cancer

Surf4, cargo trafficking, lipid metabolism, and therapeutic implications

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