| RRC ID |
55021
|
| Author |
Asakawa K, Kawakami K.
|
| Title |
Protocadherin-Mediated Cell Repulsion Controls the Central Topography and Efferent Projections of the Abducens Nucleus.
|
| Journal |
Cell Rep
|
| Abstract |
Cranial motor nuclei in the brainstem innervate diverse types of head and neck muscles. Failure in establishing these neuromuscular connections causes congenital cranial dysinnervation disorders (CCDDs) characterized by abnormal craniofacial movements. However, mechanisms that link cranial motor nuclei to target muscles are poorly understood at the molecular level. Here, we report that protocadherin-mediated repulsion mediates neuromuscular connection in the ocular motor system in zebrafish. We identify pools of abducens motor neurons that are topographically arranged according to soma size and convergently innervate a single muscle. Disruptions of Duane retraction syndrome-associated transcription factors reveal that these neurons require Mafba/MAFB, but not Sall4/SALL4, for differentiation. Furthermore, genetic perturbations of Pcdh17/protocadherin-17 result in defective axon growth and soma clumping, thereby abolishing neuromuscular connectivity. Our results suggest that protocadherin-mediated repulsion forms the central topography and efferent projection pattern of the abducens nucleus following Mafba-dependent specification and imply potential involvement of protocadherins in CCDD etiology.
|
| Volume |
24(6)
|
| Pages |
1562-1572
|
| Published |
2018-8-7
|
| DOI |
10.1016/j.celrep.2018.07.024
|
| PII |
S2211-1247(18)31114-8
|
| PMID |
30089266
|
| MeSH |
Abducens Nucleus / physiopathology*
Animals
Brain Stem / metabolism*
Humans
Zebrafish
|
| IF |
7.815
|
| Times Cited |
6
|
| Resource |
| Zebrafish |
USA:GFP
UAS:RFP
SAGFF(LF)73A
egr2b-zCre19
gSAIzGFFM1068A
gSAIzGFFM35A
gSAIzGFFM773B
HGj4A
mnGFF7
UAS:loxGloxR
UAS:loxRloxG
EGFP:UAS:pcdh17-FL-mRFP1
EGFP:UAS:pcdh17-∆CP-mRFP1
EGFP:UAS:pcdh17-∆CPT-mRFP1
actc1b:tdT-chrnd
UAS:V2V
sall4
pcdh17 |
