LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactor Ldb1, control Purkinje cell differentiation in the developing cerebellum

Zhao, Yangu; Kwan, Kin Ming; Mailloux, Christina M.; Lee, Woon Kyu; Grinberg, Alexander; Wurst, Wolfgang; Behringer, Richard R.; Westphal, Heiner

doi:10.1073/pnas.0705464104

Cited by 139 publications

(140 citation statements)

References 58 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…Although the exact topographical cell fate of caudal VZ progenitors in the Ngn1 territory has not been defined, this pattern is consistent with Ngn1 expression in newly generated Purkinje cells (Altman and Bayer, 1997). In support of this hypothesis, Ngn1 ISH signal is reported to overlap with Lhx1/5 ISH territory (Zordan et al, 2008); Lhx1/5 is expressed in differentiating Purkinje cells and is required for the normal development of these neurons (Zhao et al, 2007). However, although anti-Lhx1/5 immunolabeling reveals topographically similar immunoreactive territories in the isthmus and cerebellar anlage at E13, high magnification imaging in the confocal microscope reveals anti-Ngn1 and anti-Lhx1/5 immunosignals do not overlap.…”

Section: Ngn1 Is Expressed In Purkinje Cell Lineagesmentioning

confidence: 76%

“…2a-f). Lhx1 and Lhx5 are expressed in postmitotic, early differentiating Purkinje cells (Zhao et al, 2007) and Lhx1 and Lhx5 ISH territories partially overlap with Ngn1 in the caudal cerebellar anlage of E12.5 mice (Zordan et al, 2008). However, high magnification confocal microscopy unexpectedly reveals that Ngn1-and Lhx1/5-immunolabeled cells are distinct in both the rostral and caudal immunoreactive territories of the E13 cerebellum.…”

Section: Ngn1 Is Expressed In Two Territories In the Cerebellar Primomentioning

confidence: 89%

See 1 more Smart Citation

Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice

Lundell

Zhou

Doughty

2009

Developmental Dynamics

View full text Add to dashboard Cite

The basic helix-loop-helix (bHLH) transcription factors Ptf1a and Math1 are necessary for the specification of g-aminobutyric acid-ergic and glutamatergic cell lineages in the cerebellum, respectively. Recent evidence suggests cascades of bHLH factor activities drive cell type specificity in Ptf1a 1ve and Math1 1ve lineages. In this manuscript, we reveal cell lineages in the cerebellar cortex but not deep cerebellar nuclei express the pro-neural bHLH factor Neurogenin1 (Ngn1). Ngn1 is expressed in ventricular zone progenitors and in newly generated neurons in the caudal cerebellar primordium. In later embryonic and postnatal developmental stages, Ngn1 is expressed in progenitors and in migrating interneurons in the prospective white matter. Transgenic fate-mapping reveals Ngn1 reporter-gene expression in Purkinje cells, multiple inhibitory interneuron cell types, and in unipolar brush cells of the cortex. The data suggest Ngn1 is a component of the bHLH factor code regulating cell type specification in the cerebellar cortex. Developmental Dynamics 238:3310-3325,

show abstract

Section: Ngn1 Is Expressed In Purkinje Cell Lineagesmentioning

confidence: 76%

Section: Ngn1 Is Expressed In Two Territories In the Cerebellar Primomentioning

confidence: 89%

Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice

Lundell

Zhou

Doughty

2009

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…6 LHX1 encodes a member of a large protein family that contains the LIM domain, a unique cysteine-rich zincbinding domain. LHX1 is expressed in the brain and has been implicated in Purkinje cell development in the cerebellum 11 and in the migration of motor axons to the limbs. 12 A mouse model with a targeted mutation of LHX1 had a lack of head structures anterior to rhombomere 3 in the hindbrain.…”

Section: Discussionmentioning

confidence: 99%

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

et al. 2009

View full text Add to dashboard Cite

Deletions in chromosome 17q12 encompassing the HNF1b gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with an increased risk of epilepsy and mental retardation. We conducted a detailed clinical and molecular characterization of four patients with a deletion and five patients with a reciprocal duplication of this region. Our patients with deletion of 17q12 presented with cognitive impairment, cystic renal disease, seizures, and structural abnormalities of the brain. Patients with reciprocal duplications manifest with cognitive impairment and behavioral abnormalities, but not with seizures. Our findings expand the phenotypic spectrum associated with rearrangements of 17q12 and show that cognitive impairment is a part of the phenotype of individuals with deletions of 17q12.

show abstract

“…Lim1 was also discovered to be vital in determining the choice of spinal cord lateral motor column axon trajectory into the dorsal developing limb (Kania et al, 2000). Very recently, Lim1 and related LIM-homeobox gene Lhx5 were found to play a role in maintaining the GABAergic identity of dorsal spinal cord interneurons as well as essential factors for cerebellar Purkinje cell differentiation (Pillai et al, 2007;Zhao et al, 2007). The above-mentioned studies are informative because they illustrate examples of LIM-homeobox genes directing neuronal morphology, behavior, or differentiation without influencing initial neuronal fate specification.…”

Section: Lim1-lacz Is Expressed In Migratory Horizontal Cellsmentioning

confidence: 99%

Lim1 Is Essential for the Correct Laminar Positioning of Retinal Horizontal Cells

Poché¹,

Kwan²,

Raven³

et al. 2007

J. Neurosci.

112

View full text Add to dashboard Cite

Although much is known about the transcriptional regulation that coordinates retinal cell fate determination, very little is known about the developmental processes that establish the characteristic laminar architecture of the retina, in particular, the specification of neuronal positioning. The LIM class homeodomain transcription factor Lim1 (Lhx1) is expressed in postmitotic, differentiating, and mature retinal horizontal cells. We show that conditional ablation of Lim1 results in the ectopic localization of horizontal cells to inner aspects of the inner nuclear layer, among the retinal amacrine cells. The ectopic cells maintain a molecular phenotype consistent with horizontal cell identity; however, these neurons adopt a unique morphology more reminiscent of amacrine cells, including a dendritic arbor positioned within the inner plexiform layer. All other retinal cell populations appear unaltered. Our data suggest a model whereby Lim1 lies downstream of horizontal cell fate determination factors and functions cell autonomously to instruct differentiating horizontal cells to the appropriate laminar position in the developing retina. This study is the first to describe a cell type-specific genetic program that is essential for targeting a discrete retinal neuron population to the proper lamina.

show abstract

LIM-homeodomain proteins Lhx1 and Lhx5, and their cofactor Ldb1, control Purkinje cell differentiation in the developing cerebellum

Cited by 139 publications

References 58 publications

Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice

Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

Lim1 Is Essential for the Correct Laminar Positioning of Retinal Horizontal Cells

Contact Info

Product

Resources

About