Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord.
The ventral spinal cord generates multiple inhibitory and excitatory interneuron subtypes from four cardinal progenitor domains (p0, p1, p2, p3). Here we show that cell-cell interactions mediated by the Notch receptor play a critical evolutionarily conserved role in the generation of excitatory v2aIN and inhibitory v2bIN interneurons. Lineage-tracing experiments show that the v2aIN and v2bIN develop from genetically identical p2 progenitors. The p2 daughter cell fate is controlled by Delta4 activation of Notch receptors together with MAML factors. Cells receiving Notch signals activate a transcription factor code that specifies the v2bIN fate, whereas cells deprived of Notch signaling express another code for v2aIN formation. Thus, our study provides insight into the cell-extrinsic signaling that controls combinatorial transcription factor profiles involved in regulating the process of interneuron subtype diversification.
Peng
Chian-Yu
CY
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA.
Yajima
Hiroshi
H
Burns
Caroline Erter
CE
Zon
Leonard I
LI
Sisodia
Sangram S
SS
Pfaff
Samuel L
SL
Sharma
Kamal
K
D000818:Animals; D030801:Animals, Genetically Modified; D001973:Bromodeoxyuridine / Q000378:metabolism; D002450:Cell Communication; D002642:Chick Embryo; D018274:Electroporation / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007395:Interneurons / Q000145:classification / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology*; D015534:Trans-Activators / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D015534:Trans-Activators; D029961:Zebrafish Proteins; D001973:Bromodeoxyuridine