PMID- 36945472
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240103
DP  - 2023 Dec 28
TI  - FMRP regulates tangential neuronal migration via MAP1B.
LID - 2023.03.06.530447 [pii]
LID - 10.1101/2023.03.06.530447 [doi]
AB  - The Fragile X Syndrome (FXS) represents the most prevalent form of inherited 
      intellectual disability and is the first monogenic cause of Autism Spectrum 
      Disorder. FXS results from the absence of the RNA-binding protein FMRP (Fragile X 
      Messenger Ribonucleoprotein). Neuronal migration is an essential step of brain 
      development allowing displacement of neurons from their germinal niches to their 
      final integration site. The precise role of FMRP in neuronal migration remains 
      largely unexplored. Using live imaging of postnatal Rostral Migratory Stream 
      (RMS) neurons in Fmr1-null mice, we observed that the absence of FMRP leads to 
      delayed neuronal migration and altered trajectory, associated with defects of 
      centrosomal movement. RNA-interference-induced knockdown of Fmr1 shows that these 
      migratory defects are cell-autonomous. Notably, the primary FMRP mRNA target 
      implicated in these migratory defects is MAP1B (Microtubule-Associated Protein 
      1B). Knocking-down MAP1B expression effectively rescued most of the observed 
      migratory defects. Finally, we elucidate the molecular mechanisms at play by 
      demonstrating that the absence of FMRP induces defects in the cage of 
      microtubules surrounding the nucleus of migrating neurons, which is rescued by 
      MAP1B knockdown. Our findings reveal a novel neurodevelopmental role for FMRP in 
      collaboration with MAP1B, jointly orchestrating neuronal migration by influencing 
      the microtubular cytoskeleton.
FAU - Messaoudi, Salima
AU  - Messaoudi S
FAU - Allam, Ada
AU  - Allam A
FAU - Stoufflet, Julie
AU  - Stoufflet J
FAU - Paillard, Theo
AU  - Paillard T
FAU - Fouquet, Coralie
AU  - Fouquet C
FAU - Doulazmi, Mohamed
AU  - Doulazmi M
FAU - Le Ven, Anais
AU  - Le Ven A
FAU - Trembleau, Alain
AU  - Trembleau A
FAU - Caille, Isabelle
AU  - Caille I
LA  - eng
PT  - Preprint
DEP - 20231228
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10028813
EDAT- 2023/03/23 06:00
MHDA- 2023/03/23 06:01
PMCR- 2024/01/02
CRDT- 2023/03/22 01:57
PHST- 2023/03/23 06:00 [pubmed]
PHST- 2023/03/23 06:01 [medline]
PHST- 2023/03/22 01:57 [entrez]
PHST- 2024/01/02 00:00 [pmc-release]
AID - 2023.03.06.530447 [pii]
AID - 10.1101/2023.03.06.530447 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Dec 28:2023.03.06.530447. doi: 
      10.1101/2023.03.06.530447.