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3D reconstruction of the mouse cochlea from scRNA-seq data suggests morphogen-based principles in apex-to-base specification.
Wang, Shuze; Chakraborty, Saikat; Fu, Yujuan; Lee, Mary P; Liu, Jie; Waldhaus, Joerg.
Afiliación
  • Wang S; Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Chakraborty S; Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, USA.
  • Fu Y; Biomedical Informatics and Medical Education, University of Washington, Seattle, WA 98195, USA.
  • Lee MP; Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, USA.
  • Liu J; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Waldhaus J; Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: joergwal@med.umich.edu.
Dev Cell ; 59(12): 1538-1552.e6, 2024 Jun 17.
Article en En | MEDLINE | ID: mdl-38593801
ABSTRACT
In the mammalian auditory system, frequency discrimination depends on numerous morphological and physiological properties of the organ of Corti, which gradually change along the apex-to-base (tonotopic) axis of the organ. For example, the basilar membrane stiffness changes tonotopically, thus affecting the tuning properties of individual hair cells. At the molecular level, those frequency-specific characteristics are mirrored by gene expression gradients; however, the molecular mechanisms controlling tonotopic gene expression in the mouse cochlea remain elusive. Through analyzing single-cell RNA sequencing (scRNA-seq) data from E12.5 and E14.5 time points, we predicted that morphogens, rather than a cell division-associated mechanism, confer spatial identity in the extending cochlea. Subsequently, we reconstructed the developing cochlea in 3D space from scRNA-seq data to investigate the molecular pathways mediating positional information. The retinoic acid (RA) and hedgehog pathways were found to form opposing apex-to-base gradients, and functional interrogation using mouse cochlear explants suggested that both pathways jointly specify the longitudinal axis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cóclea Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cóclea Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos