Tlx1/3 and Ptf1a control the expression of distinct sets of transmitter and peptide receptor genes in the developing dorsal spinal cord.
Establishing the pattern of expression of transmitters and peptides as well as their receptors in different neuronal types is crucial for understanding the circuitry in various regions of the brain. Previous studies have demonstrated that the transmitter and peptide phenotypes in mouse dorsal spinal cord neurons are determined by the transcription factors Tlx1/3 and Ptf1a. Here we show that these transcription factors also determine the expression of two distinct sets of transmitter and peptide receptor genes in this region. We have screened the expression of 78 receptor genes in the spinal dorsal horn by in situ hybridization. We found that receptor genes Gabra1, Gabra5, Gabrb2, Gria3, Grin3a, Grin3b, Galr1, and Npy1r were preferentially expressed in Tlx3-expressing glutamatergic neurons and their derivatives, and deletion of Tlx1 and Tlx3 resulted in the loss of expression of these receptor genes. Furthermore, we obtained genetic evidence that Tlx3 uses distinct pathways to control the expression of receptor genes. We also found that receptor genes Grm3, Grm4, Grm5, Grik1, Grik2, Grik3, and Sstr2 were mainly expressed in Pax2-expressing GABAergic neurons in the spinal dorsal horn, and their expression in this region was abolished or markedly reduced in Ptf1a and Pax2 deletion mutant mice. Together, our studies indicate that Tlx1/3 and Ptf1a, the key transcription factors for fate determination of glutamatergic and GABAergic neurons in the dorsal spinal cord, are also responsible for controlling the expression of two distinct sets of transmitter and peptide receptor genes.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhen
Z
Guo
Congling
C
Zhao
Menggui
M
Huang
Tianwen
T
Huang
Mingran
M
Fan
Zhiqin
Z
Xie
Ying
Y
Chen
Xiaolin
X
Zhao
Guannan
G
Xia
Junlan
J
Geng
Leping
L
Cheng
D000818:Animals; D030801:Animals, Genetically Modified; D002452:Cell Count; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009496:Neurotensin / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000235:genetics; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011949:Receptors, Cholecystokinin / Q000235:genetics; D017470:Receptors, Glutamate / Q000235:genetics; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000254:growth & development* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018398:Homeodomain Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011949:Receptors, Cholecystokinin; D017470:Receptors, Glutamate; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter; C493465:Slc17a7 protein, mouse; C487378:Tlx1 protein, mouse; C487377:Tlx3 protein, mouse; D014157:Transcription Factors; D050598:Vesicular Glutamate Transport Protein 1; C062602:transcription factor PTF1; D009496:Neurotensin; D005680:gamma-Aminobutyric Acid