Ptf1a, Lbx1 and Pax2 coordinate glycinergic and peptidergic transmitter phenotypes in dorsal spinal inhibitory neurons.
Inhibitory neurons in the dorsal horn synthesize a variety of neurotransmitters, including GABA, glycine and a set of peptides. Here we show that three transcription factors, Ptf1a, Pax2, and Lbx1, which have been reported to promote a GABAergic cell fate, also specify glycinergic and peptidergic transmitter phenotypes. First, Ptf1a appears to be a master regulator, as indicated by a requirement of Ptf1a for the expression of glycinergic marker GlyT2 and a set of peptides, including neuropeptide Y (NPY), nociceptin/orphanin FQ (N/OFQ), somatostatin (SOM), enkephalin (ENK), dynorphin (DYN) and galanin (GAL). Second, Pax2 is a downstream target of Ptf1a and controls subsets of transmitter phenotypes, including the expression of GlyT2, NPY, N/OFQ, DYN, and GAL, but is dispensable for SOM or ENK expression. Third, for Lbx1, due to neuronal cell loss at late stages, our analyses focused on early embryonic stages, and we found that Lbx1 is required for the expression of GlyT2, NPY, N/OFQ and is partially responsible for SOM expression. Our studies therefore suggest a coordinated and hierarchical specification of a variety of neurotransmitters in dorsal spinal inhibitory neurons.
Huang
Menggui
M
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Huang
Tianwen
T
Xiang
Yang
Y
Xie
Zhiqin
Z
Chen
Ying
Y
Yan
Rui
R
Xu
Jianyang
J
Cheng
Leping
L
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005998:Glycine / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins / Q000096:biosynthesis; D051379:Mice; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D050487:Glycine Plasma Membrane Transport Proteins; C491868:Lbx1h protein, mouse; D009124:Muscle Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; C493270:Slc6a5 protein, mouse; D014157:Transcription Factors; C062602:transcription factor PTF1; D005680:gamma-Aminobutyric Acid; D005998:Glycine