Engrailed-2 regulates genes related to vesicle formation and transport in cerebellar Purkinje cells

Holst, Martin I.; Maercker, Christian; Pintea, Bogdan; Masseroli, Marco; Liebig, Christian; Jankowski, Jakob; Miething, Andreas; Martini, Julia; Schwaller, Beat; Oberdick, John; Schilling, Karl; Baader, Stephan L.

doi:10.1016/j.mcn.2008.04.010

Cited by 18 publications

(29 citation statements)

References 77 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Immunoblotting experiments revealed that the expression level of merlin was increased at P9 (Fig. 4 A), reflecting the results obtained by array analysis (Holst et al, 2008). As for the WT animals, the ratio between hypophosphorylated and hyperphosphorylated merlin was equal in L7En-2 mice at P9.…”

Section: Merlin Expression In a Cerebellar Mutant Deficient In Pc Densupporting

confidence: 81%

“…Because merlin expression has been described to be regulated in cerebellar tissue after overexpressing the segment polarity and autism-associated gene En-2 (Holst et al, 2008), we performed for the first time a detailed analysis of merlin expression in the CNS, in particular in the cerebellar cortex. Throughout development, merlin was clearly attributed to the gray matter and nuclear regions of the CNS in which high numbers of neurons can be found (Fig.…”

Section: Merlin Expression In Neurons Of the Murine Cnsmentioning

confidence: 99%

“…In addition, merlin has been suggested to be differentially expressed in L7En-2 mice, which are deficient in PC dendritogenesis (Baader et al, 1998;Jankowski et al, 2004;Holst et al, 2008). This implies an involvement of merlin in process outgrowth.…”

Section: Merlin Expression In a Cerebellar Mutant Deficient In Pc Denmentioning

confidence: 99%

“…We have reported recently differential expression of the tumor suppressor gene neurofibromatosis type 2 (Nf2) in developing PCs after in vivo overexpression of the transcription factor Engrailed-2 (En-2) (Holst et al, 2008). Persistent expression of En-2 has been shown to significantly delay postnatal PC dendritic development (Jankowski et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Merlin Inhibits Neurite Outgrowth in the CNS

Schulz¹,

Geißler²,

Kumar³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

The neurofibromatosis type 2 gene product merlin is known to provoke gliogenic tumors as a result of its mutagenic loss. Merlin's physiological anti-mitogenic function makes it unique among its ezrin-radixin-moesin (ERM) family members. Although ERM proteins and merlin are known to be expressed in glial cells of the peripheral nervous system and CNS, the neuronal expression pattern and function of merlin have been less well investigated. We report here expression of merlin in developing and mature neurons of the murine CNS. Within cerebellar Purkinje cells (PCs), merlin was localized in the soma, sprouting dendrites and axons. Merlin expression in PCs was high during the period of initial dendrite regression and declined during later phases of dendrite elongation. Consistently, merlin expression in vivo was increased in Engrailed-2-overexpressing PCs, which are characterized by a reduced dendritic extension. Furthermore, overexpression of merlin in dissociated cerebellar cultures and in neurogenic P19 cells caused a significant decline in neurite outgrowth, while, conversely, inhibition of merlin expression increased process formation. This effect was dependent on phosphorylation of serine 518 and involved the inactivation of the growth-promoting GTPase Rac. We thus provide evidence that merlin plays a pivotal role in controlling the neuronal wiring in the developing CNS.

show abstract

Section: Merlin Expression In a Cerebellar Mutant Deficient In Pc Densupporting

confidence: 81%

Section: Merlin Expression In Neurons Of the Murine Cnsmentioning

confidence: 99%

Section: Merlin Expression In a Cerebellar Mutant Deficient In Pc Denmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Merlin Inhibits Neurite Outgrowth in the CNS

Schulz¹,

Geißler²,

Kumar³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In fact, using ectopic overexpression of En2 (L7-En2) in cerebellar Purkinje cells during the late embryonic/early postnatal period it was shown that mossy fiber organization is disrupted (Baader et al 1999), and this has also been confirmed using conditional inactivation of the En genes (Sillitoe et al 2010). Using the L7-En2 transgenic mouse a search for target genes of En2 during the neonatal period using an array approach has revealed a major target gene cluster encoding protein and vesicle trafficking proteins, and also defects in the morphological organization of Golgi stacks and ER in the mutant were observed (Holst et al 2008). In addition, the axonal guidance factor EphA4 has emerged as a likely gene target of En2 from this and other studies, being complementary in expression pattern to En2 in wild-types and downregulated in L7-En2 mutants [ Table 2 and Suppl.…”

Section: En2 (Engrailed-2)mentioning

confidence: 83%

Analysis of Gene Networks in Cerebellar Development

Oberdick

2013

Handbook of the Cerebellum and Cerebellar Disorders

Self Cite

View full text Add to dashboard Cite

The purpose of this chapter is to provide a brief overview of the major gene networks that control cerebellum development. To simplify this task, all developmental control genes relevant to the cerebellum have been grouped into four categories based on 13 spontaneous mouse mutations with cerebellar developmental defects and for which the aberrant gene has been identified. These categories include genetic switch genes and genes for morphogenesis, physiology, and metabolism. Three distinct gene targetome studies are discussed in order to introduce some signature networks of major importance to cerebellum development based on the genetic switches En2, Atoh1 (Math1), and Rora (RORa). Similarly, array approaches have begun to reveal gene expression changes due to mutations in physiology and metabolism genes, such as Kcnj6 (Girk2) and Agtpbp1 (Nna1), respectively. These studies are revealing the interplay between transcription, morphogenetic factors, physiology, and metabolism during development. Lastly, genomics and informatics approaches are uncovering new markers of all cerebellar cell types at all stages that will be useful in the future for further clarifying the complex and often reciprocal nature of developmental mechanisms in the nervous system.

show abstract

Analysis of Gene Networks in Cerebellar Development

Oberdick

2021

Handbook of the Cerebellum and Cerebellar Disorders

Self Cite

View full text Add to dashboard Cite

The purpose of this chapter is to provide a brief overview of the major gene networks that control cerebellum development. To simplify this task, all developmental control genes relevant to the cerebellum have been grouped into four categories based on 13 spontaneous mouse mutations with cerebellar developmental defects and for which the aberrant gene has been identified. These categories include genetic switch genes and genes for morphogenesis, physiology, and metabolism. Three distinct gene targetome studies are discussed in order to introduce some signature networks of major importance to cerebellum development based on the genetic switches En2, Atoh1 (Math1), and Rora (RORα). Similarly, array approaches have begun to reveal gene expression changes due to mutations in physiology and metabolism genes, such as Kcnj6 (Girk2) and Agtpbp1 (Nna1), respectively. These studies are revealing the interplay between transcription, morphogenetic factors, physiology, and metabolism during development. Lastly, genomics and informatics approaches are uncovering new

show abstract

Engrailed-2 regulates genes related to vesicle formation and transport in cerebellar Purkinje cells

Cited by 18 publications

References 77 publications

Merlin Inhibits Neurite Outgrowth in the CNS

Merlin Inhibits Neurite Outgrowth in the CNS

Analysis of Gene Networks in Cerebellar Development

Analysis of Gene Networks in Cerebellar Development

Contact Info

Product

Resources

About