The BMP antagonist gremlin 1 contributes to the development of cortical excitatory neurons, motor balance and fear responses
| Autor: | Martin Lewis, Simon A. Koblar, Paul Q. Thomas, Susan L. Woods, Atsushi Enomoto, Ryota Ando, Nobumi Suzuki, Tongtong Wang, Krystyna A. Gieniec, Josephine A. Wright, Tamsin R M Lannagan, Laura Vrbanac, Jia Q Ng, Daniel L. Worthley, Hiroki Kobayashi, Mari Ichinose |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Mouse Biology Bone morphogenetic protein Bone Morphogenetic Protein 1 Mice 03 medical and health sciences Glutamatergic 0302 clinical medicine Conditional gene knockout medicine BMP Animals Molecular Biology Cell Proliferation Mice Knockout Motor Neurons Neurons Behavior Animal Cortical development Cerebrum Stem Cells Brain Gene Expression Regulation Developmental Cell Differentiation Fear Embryonic stem cell Cell biology Cortex (botany) Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure embryonic structures Forebrain Intercellular Signaling Peptides and Proteins Neural Development Grem1 Excitatory neuron Female Transcriptome Gremlin (protein) 030217 neurology & neurosurgery Research Article Signal Transduction Developmental Biology |
| Zdroj: | Development (Cambridge, England) article-version (VoR) Version of Record |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | Bone morphogenetic protein (BMP) signaling is required for early forebrain development and cortical formation. How the endogenous modulators of BMP signaling regulate the structural and functional maturation of the developing brain remains unclear. Here, we show that expression of the BMP antagonist Grem1 marks committed layer V and VI glutamatergic neurons in the embryonic mouse brain. Lineage tracing of Grem1-expressing cells in the embryonic brain was examined by administration of tamoxifen to pregnant Grem1creERT; Rosa26LSLTdtomato mice at 13.5 days post coitum (dpc), followed by collection of embryos later in gestation. In addition, at 14.5 dpc, bulk mRNA-seq analysis of differentially expressed transcripts between FACS-sorted Grem1-positive and -negative cells was performed. We also generated Emx1-cre-mediated Grem1 conditional knockout mice (Emx1-Cre;Grem1flox/flox) in which the Grem1 gene was deleted specifically in the dorsal telencephalon. Grem1Emx1cKO animals had reduced cortical thickness, especially layers V and VI, and impaired motor balance and fear sensitivity compared with littermate controls. This study has revealed new roles for Grem1 in the structural and functional maturation of the developing cortex. Summary: The BMP antagonist Grem1 is expressed by committed deep-layer glutamatergic neurons in the embryonic mouse cortex. Grem1 conditional knockout mice display cortical and behavioral abnormalities. |
| Databáze: | OpenAIRE |
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