Journal Mobile Options
Table of Contents
Vol. 31, No. 6, 2009
Issue release date: November 2009

Detailed Expression Pattern of Foxp1 and Its Possible Roles in Neurons of the Spinal Cord during Embryogenesis

Morikawa Y. · Komori T. · Hisaoka T. · Senba E.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


A member of winged-helix/forkhead transcription factors, Foxp1, is expressed in the developing spinal cord during mouse embryogenesis. To shed light on the potential role of Foxp1 in neurons of the developing spinal cord, we investigated the detailed expression pattern of Foxp1 between embryonic day (E) 9.5 and E17.5. At E10.25, some postmitotic neurons with strong expression of Foxp1 (Foxp1high) were first detected in the ventral half of the brachial spinal cord. By E11.5, Foxp1high neurons increased in the ventral spinal cord at the limb levels. All of Foxp1high neurons at the limb levels were Islet2+/Lhx3 motor neurons (MNs) of the lateral motor column and some neurons that expressed Foxp1 weakly (Foxp1low) at the thoracic level were MNs of the preganglionic motor column. Between E12.5 and E17.5, Foxp1low neurons were also observed in the intermediate zone throughout the ventral spinal cord, all of which were Pax2+, En1+, Evx1, Chx10, Gata3, and Lhx3 V1 interneurons. Interestingly, no colocalization of Foxp1 with Lhx3 was observed in the developing spinal cord. In addition, overexpression of Foxp1 markedly attenuated the endogenous expression of Lhx3 in a neuroendocrine cell line. Chromatin immunoprecipitation assays in a neuronal cell line and E13.5 spinal cords revealed an interaction between Foxp1 and the consensus motif in the Lhx3 promoter. These results suggest that Foxp1 may play some important roles in the determination of neuronal fates of the ventral spinal cord, possibly through the suppression of Lhx3 expression.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Allain AE, Bairi A, Meyrand P, Branchereau P (2004): Ontogenic changes of the GABAergic system in the embryonic mouse spinal cord. Brain Res 1000:134–147.
  2. Allain AE, Bairi A, Meyrand P, Branchereau P (2006): Expression of the glycinergic system during the course of embryonic development in the mouse spinal cord and its co-localization with GABA immunoreactivity. J Comp Neurol 496:832–846.
  3. Arber S, Han B, Mendelsohn M, Smith M, Jessell TM, Sockanathan S (1999): Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron 23:659–674.
  4. Arlotta P, Molyneaux BJ, Jabaudon D, Yoshida Y, Macklis JD (2008): Ctip2 controls the differentiation of medium spiny neurons and the establishment of the cellular architecture of the striatum. J Neurosci 28:622–632.
  5. Briscoe J, Pierani A, Jessell TM, Ericson J (2000): A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell 101:435–445.
  6. Burrill JD, Moran L, Goulding MD, Saueressig H (1997): PAX2 is expressed in multiple spinal cord interneurons, including a population of EN1+ interneurons that require PAX6 for their development. Development 124:4493–4503.
  7. Carlsson P, Mahlapuu M (2002): Forkhead transcription factors: key players in development and metabolism. Dev Biol 250:1–23.
  8. Cheng L, Arata A, Mizuguchi R, Qian Y, Karunaratne A, Gray PA, Arata S, Shirasawa S, Bouchard M, Luo P, Chen CL, Busslinger M, Goulding M, Onimaru H, Ma Q (2004): Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates. Nat Neurosci 7:510–517.
  9. Dasen JS, De Camilli A, Wang B, Tucker PW, Jessell TM (2008): Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1. Cell 134:304–316.
  10. Dasen JS, Liu JP, Jessell TM (2003): Motor neuron columnar fate imposed by sequential phases of Hox-c activity. Nature 425:926–933.
  11. Ferland RJ, Cherry TJ, Preware PO, Morrisey EE, Walsh CA (2003): Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain. J Comp Neurol 460:266–279.
  12. Granger A, Bleux C, Kottler ML, Rhodes SJ, Counis R, Laverriere JN (2006): The LIM-homeodomain proteins Isl-1 and Lhx3 act with steroidogenic factor 1 to enhance gonadotrope-specific activity of the gonadotropin-releasing hormone receptor gene promoter. Mol Endocrinol 20:2093–2108.
  13. Hisaoka T, Morikawa Y, Komori T, Sugiyama T, Kitamura T, Senba E (2006): Characterization of TROY-expressing cells in the developing and postnatal CNS: the possible role in neuronal and glial cell development. Eur J Neurosci 23:3149–3160.
  14. Hu H, Wang B, Borde M, Nardone J, Maika S, Allred L, Tucker PW, Rao A (2006): Foxp1 is an essential transcriptional regulator of B cell development. Nat Immunol 7:819–826.
  15. Jessell TM (2000): Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet 1:20–29.
  16. Kania A, Johnson RL, Jessell TM (2000): Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb. Cell 102:161–173.
  17. Komori T, Gyobu H, Ueno H, Kitamura T, Senba E, Morikawa Y (2008): Expression of kin of irregular chiasm-like 3/mKirre in proprioceptive neurons of the dorsal root ganglia and its interaction with nephrin in muscle spindles. J Comp Neurol 511:92–108.
  18. Lai E, Prezioso VR, Smith E, Litvin O, Costa RH, Darnell JE Jr (1990): HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally. Genes Dev 4:1427–1436.
  19. Lee SK, Pfaff SL (2001): Transcriptional networks regulating neuronal identity in the developing spinal cord. Nat Neurosci 4:1183–1191.
  20. Lumsden A (1995): Neural development. A ‘LIM code’ for motor neurons? Curr Biol 5:491–495.
  21. Matise MP, Joyner AL (1997): Expression patterns of developmental control genes in normal and Engrailed-1 mutant mouse spinal cord reveal early diversity in developing interneurons. J Neurosci 17:7805–7816.
  22. Mellon PL, Windle JJ, Goldsmith PC, Padula CA, Roberts JL, Weiner RI (1990): Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron 5:1–10.
  23. Nornes HO, Carry M (1978): Neurogenesis in spinal cord of mouse: an autoradiographic analysis. Brain Res 159:1–16.
  24. Pillai A, Mansouri A, Behringer R, Westphal H, Goulding M (2007): Lhx1 and Lhx5 maintain the inhibitory-neurotransmitter status of interneurons in the dorsal spinal cord. Development 134:357–366.
  25. Rousso DL, Gaber ZB, Wellik D, Morrisey EE, Novitch BG (2008): Coordinated actions of the forkhead protein Foxp1 and Hox proteins in the columnar organization of spinal motor neurons. Neuron 59:226–240.
  26. Shah V, Drill E, Lance-Jones C (2004): Ectopic expression of Hoxd10 in thoracic spinal segments induces motoneurons with a lumbosacral molecular profile and axon projections to the limb. Dev Dyn 231:43–56.
  27. Sharma K, Leonard AE, Lettieri K, Pfaff SL (2000): Genetic and epigenetic mechanisms contribute to motor neuron pathfinding. Nature 406:515–519.
  28. Sharma K, Sheng HZ, Lettieri K, Li H, Karavanov A, Potter S, Westphal H, Pfaff SL (1998): LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons. Cell 95:817–828.
  29. Shi C, Zhang X, Chen Z, Sulaiman K, Feinberg MW, Ballantyne CM, Jain MK, Simon DI (2004): Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1. J Clin Invest 114:408–418.
  30. Shu W, Yang H, Zhang L, Lu MM, Morrisey EE (2001): Characterization of a new subfamily of winged-helix/forkhead (Fox) genes that are expressed in the lung and act as transcriptional repressors. J Biol Chem 276:27488–27497.
  31. Takahashi K, Liu FC, Hirokawa K, Takahashi H (2003): Expression of Foxp2, a gene involved in speech and language, in the developing and adult striatum. J Neurosci Res 73:61–72.
  32. Takahashi K, Liu FC, Hirokawa K, Takahashi H (2008): Expression of Foxp4 in the developing and adult rat forebrain. J Neurosci Res 86:3106–3116.
  33. Tamura S, Morikawa Y, Iwanishi H, Hisaoka T, Senba E (2003): Expression pattern of the winged-helix/forkhead transcription factor Foxp1 in the developing central nervous system. Gene Expr Patterns 3:193–197.
  34. Tamura S, Morikawa Y, Iwanishi H, Hisaoka T, Senba E (2004): Foxp1 gene expression in projection neurons of the mouse striatum. Neuroscience 124:261–267.
  35. Tanabe Y, Jessell TM (1996): Diversity and pattern in the developing spinal cord. Science 274:1115–1123.
  36. Tsuchida T, Ensini M, Morton SB, Baldassare M, Edlund T, Jessell TM, Pfaff SL (1994): Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes. Cell 79:957–970.
  37. Wang B, Lin D, Li C, Tucker P (2003): Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors. J Biol Chem 278:24259–24268.
  38. Wang B, Weidenfeld J, Lu MM, Maika S, Kuziel WA, Morrisey EE, Tucker PW (2004): Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. Development 131:4477–4487.
  39. Weigel D, Jäckle H (1990): The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? Cell 63:455–456.
  40. Wu Y, Wang G, Scott SA, Capecchi MR (2008): Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons. Development 135:171–182.
  41. Zhadanov AB, Bertuzzi S, Taira M, Dawid IB, Westphal H (1995): Expression pattern of the murine LIM class homeobox gene Lhx3 in subsets of neural and neuroendocrine tissues. Dev Dyn 202:354–364.

Pay-per-View Options
Direct payment This item at the regular price: USD 9.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 8.00