Development, Vol 125, Issue 11 2063-2074, Copyright © 1998 by Company of Biologists

JOURNAL ARTICLES

Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development

M Grigoriou, AS Tucker, PT Sharpe and V Pachnis
Division of Developmental Neurobiology, The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.

LIM-homeobox containing (Lhx) genes encode trascriptional regulators which play critical roles in a variety of developmental processes. We have identified two genes belonging to a novel subfamily of mammalian Lhx genes, designated Lhx6 and Lhx7. Whole-mount in situ hybridisation showed that Lhx6 and Lhx7 were expressed during mouse embryogenesis in overlapping domains of the first branchial arch and the basal forebrain. More specifically, expression of Lhx6 and Lhx7 was detected prior to initiation of tooth formation in the presumptive oral and odontogenic mesenchyme of the maxillary and mandibular processes. During tooth formation, expression was restricted to the mesenchyme of individual teeth. Using explant cultures, we have shown that expression of Lhx6 and Lhx7 in mandibular mesenchyme was under the control of signals derived from the overlying epithelium; such signals were absent from the epithelium of the non-odontogenic second branchial arch. Furthermore, expression studies and bead implantation experiments in vitro have provided strong evidence that Fgf8 is primarily responsible for the restricted expression of Lhx6 and Lhx7 in the oral aspect of the maxillary and mandibular processes. In the telencephalon, expression of both genes was predominantly localised in the developing medial ganglionic eminences, flanking a Fgf8-positive midline region. We suggest that Fgf8 and Lhx6 and Lhx7 are key components of signalling cascades which determine morphogenesis and differentiation in the first branchial arch and the basal forebrain.

This article has been cited by other articles:

				F. Luzzati, L. Bonfanti, A. Fasolo, and P. Peretto DCX and PSA-NCAM Expression Identifies a Population of Neurons Preferentially Distributed in Associative Areas of Different Pallial Derivatives and Vertebrate Species Cereb Cortex, October 1, 2008; (2008) bhn145v1. [Abstract] [Full Text] [PDF]

				T. Du, Q. Xu, P. J. Ocbina, and S. A. Anderson NKX2.1 specifies cortical interneuron fate by activating Lhx6 Development, April 15, 2008; 135(8): 1559 - 1567. [Abstract] [Full Text] [PDF]

				G. Lopez-Bendito, J. A. Sanchez-Alcaniz, R. Pla, V. Borrell, E. Pico, M. Valdeolmillos, and O. Marin Chemokine Signaling Controls Intracortical Migration and Final Distribution of GABAergic Interneurons J. Neurosci., February 13, 2008; 28(7): 1613 - 1624. [Abstract] [Full Text] [PDF]

				S. J. B. Butt, I. Cobos, J. Golden, N. Kessaris, V. Pachnis, and S. Anderson Transcriptional Regulation of Cortical Interneuron Development J. Neurosci., October 31, 2007; 27(44): 11847 - 11850. [Full Text] [PDF]

				M. Fogarty, M. Grist, D. Gelman, O. Marin, V. Pachnis, and N. Kessaris Spatial Genetic Patterning of the Embryonic Neuroepithelium Generates GABAergic Interneuron Diversity in the Adult Cortex J. Neurosci., October 10, 2007; 27(41): 10935 - 10946. [Abstract] [Full Text] [PDF]

				N. Flames, R. Pla, D. M. Gelman, J. L. R. Rubenstein, L. Puelles, and O. Marin Delineation of Multiple Subpallial Progenitor Domains by the Combinatorial Expression of Transcriptional Codes J. Neurosci., September 5, 2007; 27(36): 9682 - 9695. [Abstract] [Full Text] [PDF]

				V. A. Ruzhynsky, K. A. McClellan, J. L. Vanderluit, Y. Jeong, M. Furimsky, D. S. Park, D. J. Epstein, V. A. Wallace, and R. S. Slack Cell Cycle Regulator E2F4 Is Essential for the Development of the Ventral Telencephalon J. Neurosci., May 30, 2007; 27(22): 5926 - 5935. [Abstract] [Full Text] [PDF]

				E. Colombo, P. Collombat, G. Colasante, M. Bianchi, J. Long, A. Mansouri, J. L. R. Rubenstein, and V. Broccoli Inactivation of Arx, the Murine Ortholog of the X-Linked Lissencephaly with Ambiguous Genitalia Gene, Leads to Severe Disorganization of the Ventral Telencephalon with Impaired Neuronal Migration and Differentiation J. Neurosci., April 25, 2007; 27(17): 4786 - 4798. [Abstract] [Full Text] [PDF]

				P. Liodis, M. Denaxa, M. Grigoriou, C. Akufo-Addo, Y. Yanagawa, and V. Pachnis Lhx6 Activity Is Required for the Normal Migration and Specification of Cortical Interneuron Subtypes J. Neurosci., March 21, 2007; 27(12): 3078 - 3089. [Abstract] [Full Text] [PDF]

				A. Menuet, A. Alunni, J.-S. Joly, W. R. Jeffery, and S. Retaux Expanded expression of Sonic Hedgehog in Astyanax cavefish: multiple consequences on forebrain development and evolution Development, March 1, 2007; 134(5): 845 - 855. [Abstract] [Full Text] [PDF]

				T. T. Kroll and D. D. M. O'Leary Ventralized dorsal telencephalic progenitors in Pax6 mutant mice generate GABA interneurons of a lateral ganglionic eminence fate PNAS, May 17, 2005; 102(20): 7374 - 7379. [Abstract] [Full Text] [PDF]

				A. Ohazama, S.A.C. Modino, I. Miletich, and P.T. Sharpe Stem-cell-based Tissue Engineering of Murine Teeth J. Dent. Res., July 1, 2004; 83(7): 518 - 522. [Abstract] [Full Text] [PDF]

				P. Alifragis, A. Liapi, and J. G. Parnavelas Lhx6 Regulates the Migration of Cortical Interneurons from the Ventral Telencephalon But Does Not Specify their GABA Phenotype J. Neurosci., June 16, 2004; 24(24): 5643 - 5648. [Abstract] [Full Text] [PDF]

				Q. Xu, I. Cobos, E. De La Cruz, J. L. Rubenstein, and S. A. Anderson Origins of Cortical Interneuron Subtypes J. Neurosci., March 17, 2004; 24(11): 2612 - 2622. [Abstract] [Full Text] [PDF]

				J. G. Corbin, M. Rutlin, N. Gaiano, and G. Fishell Combinatorial function of the homeodomain proteins Nkx2.1 and Gsh2 in ventral telencephalic patterning Development, October 15, 2003; 130(20): 4895 - 4906. [Abstract] [Full Text] [PDF]

				T. A. Mitsiadis, I. Angeli, C. James, U. Lendahl, and P. T. Sharpe Role of Islet1 in the patterning of murine dentition Development, September 15, 2003; 130(18): 4451 - 4460. [Abstract] [Full Text] [PDF]

				S. Nery, J. G. Corbin, and G. Fishell Dlx2 Progenitor Migration in Wild Type and Nkx2.1 Mutant Telencephalon Cereb Cortex, September 1, 2003; 13(9): 895 - 903. [Abstract] [Full Text] [PDF]

				Y. Zhao, O. Marin, E. Hermesz, A. Powell, N. Flames, M. Palkovits, J. L. R. Rubenstein, and H. Westphal The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain PNAS, July 22, 2003; 100(15): 9005 - 9010. [Abstract] [Full Text] [PDF]

				Q. Xu, E. de la Cruz, and S. A. Anderson Cortical Interneuron Fate Determination: Diverse Sources for Distinct Subtypes? Cereb Cortex, June 1, 2003; 13(6): 670 - 676. [Abstract] [Full Text] [PDF]

				O. Marin, A. S. Plump, N. Flames, C. Sanchez-Camacho, M. Tessier-Lavigne, and J. L. R. Rubenstein Directional guidance of interneuron migration to the cerebral cortex relies on subcortical Slit1/2-independent repulsion and cortical attraction Development, May 1, 2003; 130(9): 1889 - 1901. [Abstract] [Full Text] [PDF]

				Y. Chai, Y. Ito, and J. Han TGF-{beta} SIGNALINGANDITS FUNCTIONAL SIGNIFICANCEIN REGULATINGTHE FATEOF CRANIAL NEURAL CREST CELLS Crit. Rev. Oral. Biol. Med., March 1, 2003; 14(2): 78 - 88. [Abstract] [Full Text]

				C. M. Parras, C. Schuurmans, R. Scardigli, J. Kim, D. J. Anderson, and F. Guillemot Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity Genes & Dev., February 1, 2002; 16(3): 324 - 338. [Abstract] [Full Text] [PDF]

				I. Bachy, P. Vernier, and S. Retaux The LIM-Homeodomain Gene Family in the Developing Xenopus Brain: Conservation and Divergences with the Mouse Related to the Evolution of the Forebrain J. Neurosci., October 1, 2001; 21(19): 7620 - 7629. [Abstract] [Full Text] [PDF]

				H. Wichterle, D. H. Turnbull, S. Nery, G. Fishell, and A. Alvarez-Buylla In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain Development, October 1, 2001; 128(19): 3759 - 3771. [Abstract] [Full Text] [PDF]

				M. Zirlinger, G. Kreiman, and D. J. Anderson Amygdala-enriched genes identified by microarray technology are restricted to specific amygdaloid subnuclei PNAS, April 24, 2001; 98(9): 5270 - 5275. [Abstract] [Full Text] [PDF]

				S. Anderson, O Marin, C Horn, K Jennings, and J. Rubenstein Distinct cortical migrations from the medial and lateral ganglionic eminences Development, January 2, 2001; 128(3): 353 - 363. [Abstract] [PDF]

				A. Stoykova, D. Treichel, M. Hallonet, and P. Gruss Pax6 Modulates the Dorsoventral Patterning of the Mammalian Telencephalon J. Neurosci., November 1, 2000; 20(21): 8042 - 8050. [Abstract] [Full Text] [PDF]

				O. Marin, S. A. Anderson, and J. L. R. Rubenstein Origin and Molecular Specification of Striatal Interneurons J. Neurosci., August 15, 2000; 20(16): 6063 - 6076. [Abstract] [Full Text] [PDF]

				L Gunhaga, T. Jessell, and T Edlund Sonic hedgehog signaling at gastrula stages specifies ventral telencephalic cells in the chick embryo Development, January 8, 2000; 127(15): 3283 - 3293. [Abstract] [PDF]

				B. Thomas, J. Liu, J. Rubenstein, and P. Sharpe Independent regulation of Dlx2 expression in the epithelium and mesenchyme of the first branchial arch Development, January 1, 2000; 127(2): 217 - 224. [Abstract] [PDF]

				C. Ferguson, A. Tucker, and P. Sharpe Temporospatial cell interactions regulating mandibular and maxillary arch patterning Development, January 1, 2000; 127(2): 403 - 412. [Abstract] [PDF]

				Y. Zhao, Y.-J. Guo, A. C. Tomac, N. R. Taylor, A. Grinberg, E. J. Lee, S. Huang, and H. Westphal Isolated cleft palate in mice with a targeted mutation of the LIM homeobox gene Lhx8 PNAS, December 21, 1999; 96(26): 15002 - 15006. [Abstract] [Full Text] [PDF]

				A. Trumpp, M. J. Depew, J. L.R. Rubenstein, J. M. Bishop, and G. R. Martin Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch Genes & Dev., December 1, 1999; 13(23): 3136 - 3148. [Abstract] [Full Text]

				A. A. Lavdas, M. Grigoriou, V. Pachnis, and J. G. Parnavelas The Medial Ganglionic Eminence Gives Rise to a Population of Early Neurons in the Developing Cerebral Cortex J. Neurosci., September 15, 1999; 19(18): 7881 - 7888. [Abstract] [Full Text] [PDF]

				A. Sagasti, O. Hobert, E. R. Troemel, G. Ruvkun, and C. I. Bargmann Alternative olfactory neuron fates are specified by the LIM homeobox gene lim-4 Genes & Dev., July 15, 1999; 13(14): 1794 - 1806. [Abstract] [Full Text]

				S. Retaux, M. Rogard, I. Bach, V. Failli, and M.-J. Besson Lhx9: A Novel LIM-Homeodomain Gene Expressed in the Developing Forebrain J. Neurosci., January 15, 1999; 19(2): 783 - 793. [Abstract] [Full Text] [PDF]

				L Sussel, O Marin, S Kimura, and J. Rubenstein Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum Development, January 8, 1999; 126(15): 3359 - 3370. [Abstract] [PDF]

				A. Tucker, G Yamada, M Grigoriou, V Pachnis, and P. Sharpe Fgf-8 determines rostral-caudal polarity in the first branchial arch Development, January 1, 1999; 126(1): 51 - 61. [Abstract] [PDF]

				A. Tucker, A Al Khamis, C. Ferguson, I Bach, M. Rosenfeld, and P. Sharpe Conserved regulation of mesenchymal gene expression by Fgf-8 in face and limb development Development, January 1, 1999; 126(2): 221 - 228. [Abstract] [PDF]

				A. S. Tucker, K. L. Matthews, and P. T. Sharpe Transformation of Tooth Type Induced by Inhibition of BMP Signaling Science, November 6, 1998; 282(5391): 1136 - 1138. [Abstract] [Full Text]

				C. A. Ferguson, A. S. Tucker, L. Christensen, A. L. Lau, M. M. Matzuk, and P. T. Sharpe Activin is an essential early mesenchymal signal in tooth development that is required for patterning of the murine dentition Genes & Dev., August 15, 1998; 12(16): 2636 - 2649. [Abstract] [Full Text]

				M Bei and R Maas FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development Development, January 11, 1998; 125(21): 4325 - 4333. [Abstract] [PDF]