Dynamic spatiotemporal expression of LIM genes and cofactors in the embryonic and postnatal cerebral cortex

The mechanisms that regulate the development of the amygdaloid complex are as yet poorly understood. Here, we show that in the absence of the LIM-homeodomain (LIM-HD) gene Lhx2, a particular amygdaloid nucleus, the nucleus of the lateral olfactory tract (nLOT), is selectively disrupted. LIM family members are well suited for multiple roles in the development of complex structures because they participate in regulatory interactions that permit a diversity of function. To investigate the possible role for other LIM-HD genes as well as LIM-only (Lmo) genes in the developing amygdala, we examined their expression in the embryo. We show that amygdaloid nuclei upregulate distinct patterns of LIM gene expression from embryonic stages. This supports the hypothesis that LIM genes may participate in the mechanisms that control the development of the amygdala. The disruption of the nLOT in the Lhx2 mutant is the first evidence of a role for LIM-HD genes in the development of the amygdaloid complex. The combinatorial expression patterns of LIM genes suggest a comprehensive mechanism for patterning this structure.

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LIM Genes Parcellate the Embryonic Amygdala and Regulate Its Development

Remedios¹,

Subramanian²,

Tole³

2004

Section: Methodsmentioning

confidence: 99%

Selective Requirement of Pax6, But Not Emx2, in the Specification and Development of Several Nuclei of the Amygdaloid Complex

Tole¹,

Remedios²,

Saha³

et al. 2005

178

The amygdaloid complex is a group of nuclei that are thought to originate from multiple sites of the dorsal and ventral telencephalic neuroepithelium. The mechanisms that regulate their development are essentially unknown. We studied the role of Pax6 and Emx2, two transcription factors that regulate regional specification and growth of the telencephalon, in the morphogenesis of the amygdaloid complex. We used a set of specific marker genes that identify distinct amygdaloid nuclei to analyze Pax6/Small eye and Emx2 knock-out mutant mouse brains. We found that there is a selective requirement for Pax6, but not Emx2, in the formation a subset of nuclei within the amygdaloid complex. Specifically, structures that were not previously considered to be developmentally linked, the nucleus of the lateral olfactory tract and the lateral, basolateral, and basomedial nuclei, all appear to have a common requirement for Pax6. Together, our findings provide new insights into the origins and mechanisms underlying the development of the amygdaloid complex.

“…This pattern is consistent with previous findings describing weak Lhx2 mRNA expression in rostromedial thalamic nuclei, including the dLG and VP nuclei (Nakagawa and O'Leary, 2001). Interestingly, a graded distribution of Lhx2 mRNA and protein has been also demonstrated in the developing cortical ventricular zone, which is essential for the formation of cortical structures (Porter et al, 1997;Donoghue and Rakic, 1999;Nakagawa et al, 1999;Rétaux et al, 1999;Bulchand et al, 2003). Moreover, Bmp4 and Bmp2-derived molecules from the roof plate are shown to regulate Lhx2 cortical gradient (Monuki et al, 2001).…”

Section: Dynamic Regulation Of Lhx2 In Postmitotic Thalamic Neuronsmentioning

confidence: 99%

TheLhx2Transcription Factor Controls Thalamocortical Axonal Guidance by Specific Regulation of Robo1 and Robo2 Receptors

Marcos-Mondéjar

Peregrín²,

Li³

et al. 2012

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.