PMID:22457488

Citation	Marcos-Mondéjar, P, Peregrín, S, Li, JY, Carlsson, L, Tole, S and López-Bendito, G (2012) The lhx2 transcription factor controls thalamocortical axonal guidance by specific regulation of robo1 and robo2 receptors. J. Neurosci. 32:4372-85
Abstract	The assembly of neural circuits is dependent upon the generation of specific neuronal subtypes, each subtype displaying unique properties that direct the formation of selective connections with appropriate target cells. Actions of transcription factors in neural progenitors and postmitotic cells are key regulators in this process. LIM-homeodomain transcription factors control crucial aspects of neuronal differentiation, including subtype identity and axon guidance. Nonetheless, their regulation during development is poorly understood and the identity of the downstream molecular effectors of their activity remains largely unknown. Here, we demonstrate that the Lhx2 transcription factor is dynamically regulated in distinct pools of thalamic neurons during the development of thalamocortical connectivity in mice. Indeed, overexpression of Lhx2 provokes defective thalamocortical axon guidance in vivo, while specific conditional deletion of Lhx2 in the thalamus produces topographic defects that alter projections from the medial geniculate nucleus and from the caudal ventrobasal nucleus in particular. Moreover, we demonstrate that Lhx2 influences axon guidance and the topographical sorting of axons by regulating the expression of Robo1 and Robo2 guidance receptors, which are essential for these axons to establish correct connections in the cerebral cortex. Finally, augmenting Robo1 function restores normal axon guidance in Lhx2-overexpressing neurons. By regulating axon guidance receptors, such as Robo1 and Robo2, Lhx2 differentially regulates the axon guidance program of distinct populations of thalamic neurons, thus enabling the establishment of specific neural connections.
Links	PubMed Online version:10.1523/JNEUROSCI.5851-11.2012
Keywords	Animals; Axons/physiology; Cerebral Cortex/growth & development; Cerebral Cortex/metabolism; Cerebral Cortex/physiology; Embryo, Mammalian; Gene Deletion; Gene Expression Regulation, Developmental; LIM-Homeodomain Proteins/metabolism; LIM-Homeodomain Proteins/physiology; Mice; Mice, Inbred ICR; Mice, Knockout; Mice, Transgenic; Nerve Tissue Proteins/biosynthesis; Neural Pathways/growth & development; Neural Pathways/metabolism; Neural Pathways/physiology; Neurogenesis/physiology; Receptors, Immunologic/biosynthesis; Signal Transduction/physiology; Thalamus/growth & development; Thalamus/metabolism; Thalamus/physiology; Transcription Factors/metabolism; Transcription Factors/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:LHX2		GO:0045892: negative regulation of transcription, DNA-dependent	ECO:0000315:		P		Fig 4 shows that in thalamic-projecting neurons, LHX2 regulates the expression of ROBO1 and ROBO2.	complete CACAO 6353
MOUSE:LHX2		GO:0007411: axon guidance	ECO:0000315:		P		Fig. 3 shows that normal levels of LHX2 in the thalamus regulate axon guidance.	complete CACAO 6354
MOUSE:LHX2	involved_in	GO:0007411: axon guidance	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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