GDF15 controls primary cilia morphology and function thereby affecting progenitor proliferation.

Baur, Katja; San, Seydanur; Hölzl-Wenig, Gabriele; Mandl, Claudia; Hellwig, Andrea; Ciccolini, Francesca

Baur, Katja; San, Seydanur; Hölzl-Wenig, Gabriele; Mandl, Claudia; Hellwig, Andrea; Ciccolini, Francesca.

Afiliación

Baur K; https://ror.org/038t36y30 Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), Heidelberg University, Heidelberg, Germany.
San S; https://ror.org/038t36y30 Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), Heidelberg University, Heidelberg, Germany.
Hölzl-Wenig G; Sorbonne University, Paris, France.
Mandl C; https://ror.org/038t36y30 Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), Heidelberg University, Heidelberg, Germany.
Hellwig A; https://ror.org/038t36y30 Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), Heidelberg University, Heidelberg, Germany.
Ciccolini F; https://ror.org/038t36y30 Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), Heidelberg University, Heidelberg, Germany.

Life Sci Alliance ; 7(7)2024 Jul.

Article en En | MEDLINE | ID: mdl-38719753

ABSTRACT

ABSTRACT

We recently reported that growth/differentiation factor 15 (GDF15) and its receptor GDNF family receptor alpha-like (GFRAL) are expressed in the periventricular germinal epithelium thereby regulating apical progenitor proliferation. However, the mechanisms are unknown. We now found GFRAL in primary cilia and altered cilia morphology upon GDF15 ablation. Mutant progenitors also displayed increased histone deacetylase 6 (Hdac6) and ciliary adenylate cyclase 3 (Adcy3) transcript levels. Consistently, microtubule acetylation, endogenous sonic hedgehog (SHH) activation and ciliary ADCY3 were all affected in this group. Application of exogenous GDF15 or pharmacological antagonists of either HDAC6 or ADCY3 similarly normalized ciliary morphology, proliferation and SHH signalling. Notably, Gdf15 ablation affected Hdac6 expression and cilia length only in the mutant periventricular niche, in concomitance with ciliary localization of GFRAL. In contrast, in the hippocampus, where GFRAL was not expressed in the cilium, progenitors displayed altered Adcy3 expression and SHH signalling, but Hdac6 expression, cilia morphology and ciliary ADCY3 levels remained unchanged. Thus, ciliary signalling underlies the effect of GDF15 on primary cilia elongation and proliferation in apical progenitors.

Asunto(s)

Adenilil Ciclasas; Proliferación Celular; Cilios; Proteínas Hedgehog; Histona Desacetilasa 6; Transducción de Señal; Animales; Ratones; Acetilación; Adenilil Ciclasas/metabolismo; Adenilil Ciclasas/genética; Proliferación Celular/genética; Cilios/metabolismo; Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo; Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/genética; Proteínas Hedgehog/metabolismo; Proteínas Hedgehog/genética; Histona Desacetilasa 6/metabolismo; Histona Desacetilasa 6/genética; Ratones Noqueados; Células Madre/metabolismo; Células Madre/citología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Adenilil Ciclasas / Cilios / Proliferación Celular / Proteínas Hedgehog / Histona Desacetilasa 6 Límite: Animals Idioma: En Revista: Life Sci Alliance Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

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