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Mouse hippocampi transcriptomics of Daam1 microexon KO (RNA-seq)

ABSTRACT: To investigate the impact of Daam1 microexon removal on hippocampal function, we have generated RNA-seq data from adult male mice. Actin cytoskeleton dynamics is crucial for neurogenesis and neuronal function. Precise quantitative and qualitative regulation of actin polymerization is achieved by multiple actin-binding proteins, among which formins are particularly versatile. Here, we investigate how neuronal-specific splicing expands formin's functional diversity in the brain. We uncovered a highly conserved microexon in DAAM1 that extends the linker region of its FH2 domain, leading to remarkable changes in actin polymerization rates and structure. Microexon deletion causes neuritogenesis defects and increased calcium influx in in vitro differentiated mouse neurons, and mice carrying this deletion exhibit deficient long-term memory formation. These memory defects were associated with higher activity of DAAM1's interactor RhoA, increased ARC protein levels, postsynaptic deficiencies, fewer dendritic spines and impaired long-term potentiation. In summary, precise post-transcriptional regulation of DAAM1's FH2 domain is a novel mechanism for modulating actin polymerization in neural spinesneurons and is essential for proper brain function.

ORGANISM(S): Mus musculus

PROVIDER: GSE219244 | GEO | 2025/03/14

REPOSITORIES: GEO

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