Characterization of Foxp2-expressing cells in the developing spinal cord
Abstract
Two members of winged-helix/forkhead transcription factors, Foxp1 and Foxp2, are expressed in the developing and adult CNS, including the striatum, cerebral cortex, and thalamus. In a previous study, we have demonstrated that Foxp1 is expressed in a subpopulation of V1 interneurons in addition to motor neurons of the spinal cord during mouse embryogenesis. However, the detailed expression pattern of Foxp2 and its relationship with Foxp1 in the developing spinal cord remains to be elucidated. To shed light on the potential roles of Foxp1 and Foxp2 in the developing spinal cord, we characterized Foxp2-expressing cells during mouse embryogenesis. At embryonic day (E) 11.0, Foxp2-expressing cells were first observed in the ventral spinal cord, which were Pax6(-), p27(+), and neuron-specific class III beta-tubulin(+) postmitotic neurons. Between E13.5 and E15.5, high expression of Foxp2 was observed in both medial and lateral parts of the ventral spinal cord. Double-immunofluorescence staining for Foxp2 with some homeodomain transcription factors revealed that Foxp2-expressing neurons were Pax2(+), En1(+), Evx1(-), Chx10(-), Gata3(-), and Lhx3(-) V1 interneurons in the intermediate zone throughout the ventral spinal cord, indicating that Foxp2-expressing neurons were also V1 interneurons with the same phenotypes as Foxp1-expressing interneurons. In addition, neither Foxp1 nor Foxp2 was expressed in ventral calbindin(+) Renshaw cells. However, Foxp2 did not colocalize with Foxp1 in interneurons of the ventral spinal cord. These findings suggest that Foxp1 and Foxp2 are expressed in the distinct subsets of V1 interneurons that belong to non-Renshaw cells in the ventral spinal cord during embryogenesis. Thus, Foxp1 and Foxp2 may be involved in the determination of the cell type identities during late embryogenesis: the classes of neurotransmitters and the functional subtypes of non-Renshaw cells, such as Ia and Ib inhibitory interneurons.
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The differential gene expression analysis recovered multiple TFs with well-established differential expression patterns, including Shox2 in V2a neurons, Foxp2 in V1 neurons, Lhx4 in MNs and V2a neurons, Neurog3 and Uncx in V3 neurons, and high levels of Nr2f2, Nfia, Foxp1 and Creb5 in MNs.
“This recovered multiple TFs, many with well-established differential gene expression patterns, for example: Shox2 in V2a neurons”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Morikawa et al., 2009
Cites
1 retracted
Lu, M. M., Li, S., Yang, H., et al. (2002) · Gene Expression Patterns · doi:10.1016/s1567-133x(02)00058-3 · Cited by 37 · see citing works
RetractedNeuronal specification in the spinal cord: inductive signals and transcriptional codes
Jessell, T. M. (2000) · Nature Reviews Genetics · doi:10.1038/35049541 · Cited by 2,089 · see citing works
A forkhead-domain gene is mutated in a severe speech and language disorder
Lai, C. S. L., Fisher, S. E., Hurst, J. A., Vargha‐Khadem, F., & Monaco, A. P. (2001) · Nature · doi:10.1038/35097076 · Cited by 2,053 · see citing works
The cytoarchitectonic organization of the spinal cord in the cat
Rexed, B. (1952) · The Journal of Comparative Neurology · doi:10.1002/cne.900960303 · Cited by 1,633 · see citing works
Briscoe, J., Pierani, A., Jessell, T. M., & Ericson, J. (2000) · Cell · doi:10.1016/s0092-8674(00)80853-3 · Cited by 1,111 · see citing works
Forkhead Transcription Factors: Key Players in Development and Metabolism
Carlsson, P., & Mahlapuu, M. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0780 · Cited by 842 · see citing works
Five years on the wings of fork head
Kaufmann, E., & Knöchel, W. (1996) · Mechanisms of Development · doi:10.1016/0925-4773(96)00539-4 · Cited by 660 · see citing works
Winged helix transcription factor BF-1 is essential for the development of the cerebral hemispheres
Xuan, S., Baptista, C., Balas, G., Tao, W., Soares, V. C., & Lai, E. (1995) · Neuron · doi:10.1016/0896-6273(95)90262-7 · Cited by 603 · see citing works
Lee, M. K., Tuttle, J. B., Rebhun, L. I., Cleveland, D. W., & Frankfurter, A. J. (1990) · Cell Motility and the Cytoskeleton · doi:10.1002/cm.970170207 · Cited by 593 · see citing works
Common Principles of Motor Control in Vertebrates and Invertebrates
Pearson, K. G. (1993) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.16.030193.001405 · Cited by 567 · see citing works
Organization in the Spinal Cord
Brown, A. G. (1981) · Springer eBooks · doi:10.1007/978-1-4471-1305-8 · Cited by 524 · see citing works
Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain
Ferland, R. J., Cherry, T. J., Preware, P. O., Morrisey, E. E., & Walsh, C. A. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10654 · Cited by 477 · see citing works
Mizuguchi, R., Sugimori, M., Takebayashi, H., Kosako, H., Nagao, M., Yoshida, S., Nabeshima, Y., Shimamura, K., & Nakafuku, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00413-5 · Cited by 471 · see citing works
The fork head domain: A novel DNA binding motif of eukaryotic transcription factors?
Weigel, D., & Jäckle, H. (1990) · Cell · doi:10.1016/0092-8674(90)90439-l · Cited by 463 · see citing works
Lai, E., Prezioso, V. R., Smith, E., Litvin, O., Costa, R. H., & Darnell, J. E., Jr. (1990) · Genes & Development · doi:10.1101/gad.4.8.1427 · Cited by 461 · see citing works
Lanuza, G. M., Gosgnach, S., Pierani, A., Jessell, T. M., & Goulding, M. (2004) · Neuron · doi:10.1016/s0896-6273(04)00249-1 · Cited by 450 · see citing works
Tao, W., & Lai, E. (1992) · Neuron · doi:10.1016/0896-6273(92)90210-5 · Cited by 415 · see citing works
Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord
Gross, M. K., Dottori, M., & Goulding, M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00690-6 · Cited by 396 · see citing works
Control of Interneuron Fate in the Developing Spinal Cord by the Progenitor Homeodomain Protein Dbx1
Pierani, A., Moran-Rivard, L., Sunshine, M. J., Littman, D. R., Goulding, M., & Jessell, T. M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00212-4 · Cited by 379 · see citing works
Dasen, J. S., De Camilli, A., Wang, B., Tucker, P. W., & Jessell, T. M. (2008) · Cell · doi:10.1016/j.cell.2008.06.019 · Cited by 376 · see citing works
Crone, S. A., Quinlan, K. A., Zagoraiou, L., Droho, S., Restrepo, C. E., Lundfald, L., Endo, T., Setlak, J., Jessell, T. M., Kiehn, O., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.08.009 · Cited by 358 · see citing works
Shu, W., Yang, H., Zhang, L., Lu, M. M., & Morrisey, E. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100636200 · Cited by 353 · see citing works
V3 Spinal Neurons Establish a Robust and Balanced Locomotor Rhythm during Walking
Zhang, Y., Narayan, S., Geiman, E. J., Lanuza, G. M., Velasquez, T., Shanks, B., Akay, T., Dyck, J. R. B., Pearson, K. G., Gosgnach, S., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.027 · Cited by 350 · see citing works
Lai, E., Clark, K. L., Burley, S. K., & Darnell, J. E., Jr. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10421 · Cited by 327 · see citing works
Crossinhibitory Activities of Ngn1 and Math1 Allow Specification of Distinct Dorsal Interneurons
Gowan, K., Helms, A. W., Hunsaker, T., Collisson, T., Ebert, P. J., Odom, R., & Johnson, J. E. B. (2001) · Neuron · doi:10.1016/s0896-6273(01)00367-1 · Cited by 302 · see citing works
Transcriptional networks regulating neuronal identity in the developing spinal cord
Lee, S., & Pfaff, S. L. (2001) · Nature Neuroscience · doi:10.1038/nn750 · Cited by 290 · see citing works
Groszer, M., Keays, D. A., Deacon, R. M. J., de Bono, J. P., Prasad-Mulcare, S., Gaub, S., Baum, M. G., French, C. A., Nicod, J., Coventry, J. A., et al. (2008) · Current Biology · doi:10.1016/j.cub.2008.01.060 · Cited by 281 · see citing works
Evx1 Is a Postmitotic Determinant of V0 Interneuron Identity in the Spinal Cord
Moran-Rivard, L., Kagawa, T., Saueressig, H., Gross, M. K., Burrill, J. D., & Goulding, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00213-6 · Cited by 261 · see citing works
de Oliveira, A. L. R., Hydling, F., Olsson, E., Shi, T.-J. S., Edwards, R. H., Fujiyama, F., Kaneko, T., Hökfelt, T. G. M., Cullheim, S., & Meister, B. (2003) · Synapse · doi:10.1002/syn.10249 · Cited by 260 · see citing works
Rousso, D. L., Gaber, Z. B., Wellik, D. M., Morrisey, E. E., & Novitch, B. G. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.025 · Cited by 254 · see citing works
Postnatal phenotype and localization of spinal cord V1 derived interneurons
Alvarez, F. J., Jonas, P. C., Sapir, T., Hartley, R., Berrocal, M. C., Geiman, E. J., Todd, A. J., & Goulding, M. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20711 · Cited by 243 · see citing works
Fujita, E., Tanabe, Y., Shiota, A., Ueda, M., Suwa, K., Momoi, M. Y., & Momoi, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712298105 · Cited by 233 · see citing works
Burrill, J. D., Moran, L., Goulding, M., & Saueressig, H. (1997) · Development · doi:10.1242/dev.124.22.4493 · Cited by 210 · see citing works
Sugimori, M., Nagao, M., Bertrand, N., Parras, C., Guillemot, F., & Nakafuku, M. (2007) · Development · doi:10.1242/dev.001255 · Cited by 197 · see citing works
Hanashima, C., Shen, L., Li, S. C., & Lai, E. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-15-06526.2002 · Cited by 194 · see citing works
Neurogenesis in spinal cord of mouse: an autoradiographic analysis
Nornes, H. O., & Carry, M. (1978) · Brain Research · doi:10.1016/0006-8993(78)90105-1 · Cited by 191 · see citing works
Pax6 and Engrailed 1 Regulate Two Distinct Aspects of Renshaw Cell Development
Sapir, T., Geiman, E. J., Wang, Z., Velasquez, T., Mitsui, S., Yoshihara, Y., Frank, E., Álvarez, F. J., & Goulding, M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3187-03.2004 · Cited by 189 · see citing works
Saueressig, H., Burrill, J. D., & Goulding, M. (1999) · Development · doi:10.1242/dev.126.19.4201 · Cited by 188 · see citing works
Patterning cell types in the dorsal spinal cord: what the mouse mutants say
Caspary, T., & Anderson, K. V. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1073 · Cited by 187 · see citing works
Lundfald, L., Restrepo, C. E., Butt, S. J. B., Peng, C., Droho, S., Endo, T., Zeilhofer, H. U., Sharma, K., & Kiehn, O. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05906.x · Cited by 172 · see citing works
Expression of Foxp2, a gene involved in speech and language, in the developing and adult striatum
Takahashi, K., Liu, F., Hirokawa, K., & Takahashi, H. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10638 · Cited by 162 · see citing works
Lhx1andLhx5maintain the inhibitory-neurotransmitter status of interneurons in the dorsal spinal cord
Pillai, A., Mansouri, A., Behringer, R. R., Westphal, H., & Goulding, M. (2006) · Development · doi:10.1242/dev.02717 · Cited by 138 · see citing works
Heterogeneity of V2‐derived interneurons in the adult mouse spinal cord
Al‐Mosawie, A., Wilson, J. M. M., & Brownstone, R. M. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05907.x · Cited by 136 · see citing works
Matise, M. P., & Joyner, A. L. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-20-07805.1997 · Cited by 132 · see citing works
Organization of the spinal cord
Eccles, J. C., & Schadé, J. P. (1964) · Cited by 131 · see citing works
Lu, M. M., Li, S., Yang, H., & Morrisey, E. E. (2002) · Mechanisms of Development · doi:10.1016/s0925-4773(03)00116-3 · Cited by 120 · see citing works
Labosky, P. A., Winnier, G. E., Jetton, T. L., Hargett, L. K., Ryan, A. K., Rosenfeld, M. G., Parlow, A. F., & Hogan, B. L. M. (1997) · Development · doi:10.1242/dev.124.7.1263 · Cited by 104 · see citing works
Calbindin D28k expression in immunohistochemically identified Renshaw cells
Carr, P. A., Álvarez, F. J., Leman, E. A., & Fyffe, R. E. W. (1998) · Neuroreport · doi:10.1097/00001756-199808030-00043 · Cited by 98 · see citing works
Jankowska, E., & Hammar, I. (2002) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00185-6 · Cited by 96 · see citing works
Foxp1 gene expression in projection neurons of the mouse striatum
Tamura, S., Morikawa, Y., Iwanishi, H., Hisaoka, T., & Senba, E. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.11.036 · Cited by 92 · see citing works
Self-citationLi, S., Misra, K., Matise, M. P., & Xiang, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504799102 · Cited by 84 · see citing works
Essential Function of Oncostatin M in Nociceptive Neurons of Dorsal Root Ganglia
Morikawa, Y., Tamura, S., Minehata, K.-I., Donovan, P. J., Miyajima, A., & Senba, E. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4975-03.2004 · Cited by 80 · see citing works
Self-citationFkh5 -deficient mice show dysgenesis in the caudal midbrain and hypothalamic mammillary body
Wehr, R., Mansouri, A., de Maeyer, T., & Gruß, P. (1997) · Development · doi:10.1242/dev.124.22.4447 · Cited by 70 · see citing works
Wenner, P., O'Donovan, M. J., & Matise, M. P. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.84.5.2651 · Cited by 70 · see citing works
Expression of Foxp4 in the developing and adult rat forebrain
Takahashi, K., Liu, F., Hirokawa, K., & Takahashi, H. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21770 · Cited by 60 · see citing works
Tamura, S., Morikawa, Y., & Senba, E. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.09.021 · Cited by 60 · see citing works
Self-citationProx1 regulates a transitory state for interneuron neurogenesis in the spinal cord
Mishra, K., Gui, H., & Matise, M. P. (2008) · Developmental Dynamics · doi:10.1002/dvdy.21422 · Cited by 56 · see citing works
Álvarez-Bolado, G., Zhou, X., Voss, A. K., Thomas, T., & Gruß, P. (2000) · Development · doi:10.1242/dev.127.5.1029 · Cited by 51 · see citing works
Allain, A., Baı̈ri, A., Meyrand, P., & Branchereau, P. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.20967 · Cited by 48 · see citing works
Tamura, S., Morikawa, Y., Iwanishi, H., Hisaoka, T., & Senba, E. (2003) · Gene Expression Patterns · doi:10.1016/s1567-133x(03)00003-6 · Cited by 45 · see citing works
Self-citationOntogenic changes of the GABAergic system in the embryonic mouse spinal cord
Allain, A., Baı̈ri, A., Meyrand, P., et al. (2004) · Brain Research · doi:10.1016/j.brainres.2003.11.071 · Cited by 43 · see citing works
A Dorsal Elaboration in the Spinal Cord
Matise, M. P. (2002) · Neuron · doi:10.1016/s0896-6273(02)00710-9 · Cited by 25 · see citing works
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Lai, H. C., Seal, R. P., & Johnson, J. E. (2016) · Development · doi:10.1242/dev.139592 · Cited by 188 · see citing works
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Francius, C., Harris, A., Rucchin, V., Hendricks, T. J., Stam, F. J., Barber, M., Kurek, D., Grosveld, F. G., Pierani, A., Goulding, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070325 · Cited by 97 · see citing works
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- Authors
- Morikawa, Y., Hisaoka, T., & Senba, E.
- Affiliations
- Wakayama Medical University (JP)
- Corresponding author
- Morikawa, Y.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 162
- Issue
- 4
- Pages
- 1150-1162
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1974706154
- Cited by
- 33
- References
- 62
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 5 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wakayama Medical University
- Ministry of Education, Culture, Sports, Science and Technology (17700337)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- FOXP2, FOXP1, spinal cord development, ventral spinal cord, Renshaw cells, intermediate zone, cell identity, inhibitory interneurons, PAX2, EN1, postmitotic neurons
- MeSH terms
- Animals, Interneurons, Mice, Inbred C57BL, Repressor Proteins, Spinal Cord, Mice, Forkhead Transcription Factors
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