Regulation of chandelier cell cartridge and bouton development via DOCK7-mediated ErbB4 activation.
Chandelier cells (ChCs), typified by their unique axonal morphology, are the most distinct interneurons present in cortical circuits. Via their distinctive axonal terminals, called cartridges, these cells selectively target the axon initial segment of pyramidal cells and control action potential initiation; however, the mechanisms that govern the characteristic ChC axonal structure have remained elusive. Here, by employing an in utero electroporation-based method that enables genetic labeling and manipulation of ChCs in vivo, we identify DOCK7, a member of the DOCK180 family, as a molecule essential for ChC cartridge and bouton development. Furthermore, we present evidence that DOCK7 functions as a cytoplasmic activator of the schizophrenia-associated ErbB4 receptor tyrosine kinase and that DOCK7 modulates ErbB4 activity to control ChC cartridge and bouton development. Thus, our findings define DOCK7 and ErbB4 as key components of a pathway that controls the morphological differentiation of ChCs, with implications for the pathogenesis of schizophrenia.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Yilin
Y
Tai
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Justyna A
JA
Janas
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Chia-Lin
CL
Wang
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address: vanaelst@cshl.edu.
Linda
L
Van Aelst
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D051379:Mice; D017729:Presynaptic Terminals / Q000378:metabolism*; D066247:Receptor, ErbB-4
C539620:Dock7 protein, mouse; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4