<i>En1</i> is necessary for survival of neurons in the ventral nuclei of the lateral lemniscus

Altieri, Stefanie C.; Zhao, Tao; Jalabi, Walid; Romito-DiGiacomo, Rita R.; Maricich, Stephen M.

doi:10.1002/dneu.22388

Cited by 12 publications

(22 citation statements)

References 47 publications

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“…The b1r4-Cre is a transgenic mouse line that has been obtained using a well-characterized r4 enhancer from the Hoxb1 locus (Studer et al 1994 ) to express the Cre -recombinase gene exclusively in r4. This contrasts with the previous lines Hoxb1 Cre (Altieri et al 2016 ; Arenkiel et al 2003 ; Farago et al 2006 ; Maricich et al 2009 ; Marrs et al 2013 ) and r4-Cre (Geisen et al 2008 ; Oury et al 2006 ) which were described as r4-specific lines, though they invariably also display additional Cre expression caudal to r4. In the CNS, no ectopic Cre expression has been observed in the transgenic b1r4-Cre so far (Di Bonito et al 2013a ; their Figure S1D, and data not shown), but the theoretic possibility of some ectopic expression cannot be fully discounted.…”

Section: Introductionmentioning

confidence: 76%

“…Its dorsoventral origin within r4 is suggested by the facts that VLL cells share a GABAergic/glycinergic phenotype (e.g. expression of GlyT2, GAD67, VIAAT ) with neurons in the lateral, ventral and medial nuclei of the trapezoid body, and both VLL and the trapezoid complex derive from an En1Cre genetic lineage (Altieri et al 2015 , 2016 ). The latter is topographically restricted to the basal plate, which indicates that the VLL migration probably has a basal origin.…”

Section: Discussionmentioning

confidence: 99%

“…In mouse, the use of the Cre–lox system and of various Cre-recombinase lines, either specific to distinct rhombomeres (Altieri et al 2015 ; Di Bonito et al 2013a , 2015 ; Di Meglio et al 2013 ; Farago et al 2006 ; Jensen et al 2008 ; Maricich et al 2009 ; Oury et al 2006 ; Pasqualetti et al 2007 ), or to specific DV subdomains (Altieri et al 2016 ; Fujiyama et al 2009 ; Kim et al 2008 ; Marrs et al 2013 ; Rose et al 2009 ; Storm et al 2009 ; Wang et al 2005 ), have been instrumental in mapping the origin of some hindbrain neuronal subtypes, eventually following their migratory displacements during development and their projections. However, only few rhombomere-specific lines including Rse-Cre (r2) (Awatramani et al 2003 ), Krox20 Cre or Egr2 Cre (r3/r5) (Voiculescu et al 2000 ), Hoxb1 Cre (r4 to posterior) (Arenkiel et al 2003 ) and Hoxa3-Cre (r5/r6) (Di Meglio et al 2013 ) have been used to dissect the assembly of sensorimotor systems.…”

Section: Introductionmentioning

confidence: 99%

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Nuclear derivatives and axonal projections originating from rhombomere 4 in the mouse hindbrain

2017

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The r4-derived territory is located in the pontine region of the brainstem, forming a wedge-shaped slice that broadens from the choroidal roof to the ventral midline. R4-derived neuronal populations migrate radially inside and tangentially outside this rhombomere, forming nuclei of the sensorimotor auditory, vestibular, trigeminal and reticular systems. R4-derived fibre tracts contribute to the lateral lemniscus, the trigeminothalamic tracts, the medial tegmental tract and the medial forebrain bundle, which variously project to the midbrain, thalamus, hypothalamus and telencephalon. Other tracts such as the trigeminocerebellar and vestibulocerebellar tracts reach the cerebellum, while the medial and lateral vestibulospinal tracts, and the reticulospinal and trigeminal oro-spinal tracts extend into the spinal cord. Many r4-derived fibres are crossed; they decussate to the contralateral side traversing the midline through the cerebellar, collicular and intercollicular commissures, as well as the supraoptic decussation. Moreover, some fibres enter into the posterior and anterior commissures and some terminals reach the septum. Overall, this study provides an overview of all r4 neuronal populations and axonal tracts from their embryonic origin to the adult final location and target.

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Section: Introductionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nuclear derivatives and axonal projections originating from rhombomere 4 in the mouse hindbrain

2017

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“…More complete depiction of En1‐negative cell structure is necessary to resolve whether a non‐principal neuron class exists within the mouse MNTB, noting that non‐principal cells may also be En1‐positive. The En1‐Cre line may also be useful for genetic manipulation of neurons in other brain regions, including the superior and inferior colliculi, cerebellum, reticular formation, spinal cord (V1 interneurons), ventral nucleus of the trapezoid body, ventral nucleus of the lateral lemniscus and lateral nucleus of the trapezoid body (Saueressig et al, ; Marrs et al, ; Altieri et al, ). For studies of globular busy cell innervation of MNTB, the En1‐Cre line is a useful tool for selective manipulation of the postsynaptic neuron.…”

Section: Discussionmentioning

confidence: 99%

Glial Cell Expansion Coincides with Neural Circuit Formation in the Developing Auditory Brainstem

Brandebura

Morehead

Heller

et al. 2018

Developmental Neurobiology

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Neural circuit formation involves maturation of neuronal, glial and vascular cells, as well as cell proliferation and cell death. A fundamental understanding of cellular mechanisms is enhanced by quantification of cell types during key events in synapse formation and pruning and possessing qualified genetic tools for cell type-specific manipulation. Acquiring this information in turn requires validated cell markers and genetic tools. We quantified changing proportions of neurons, astrocytes, oligodendrocytes, and microglia in the medial nucleus of the trapezoid body (MNTB) during neural circuit development. Cell type-specific markers, light microscopy and 3D virtual reality software, the latter developed in our laboratory, were used to count cells within distinct cell populations at postnatal days (P)3 and P6, bracketing the period of nerve terminal growth and pruning in this system. These data revealed a change from roughly equal numbers of neurons and glia at P3 to a 1.5:1 ratio of glia to neurons at P6. PCNA and PH3 labeling revealed that proliferation of oligodendrocytes contributed to the increase in glial cell number during this timeframe. We next evaluated Cre driver lines for selectivity in labeling cell populations. En1-Cre was specific for MNTB neurons. PDGFRα-Cre and Aldh1L1-Cre, thought to be mostly specific for oligodendrocyte lineage cells and astrocytes, respectively, both labeled significant numbers of neurons, oligodendrocytes, and astrocytes and are non-specific genetic tools in this neural system.

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“…In summary, our data add Crygn to genes such as Cacna1c [ 21 ], Cacna1d [ 22 ], contactin-5 [ 34 ] or En1 [ 57 , 58 ], that are important for maintenance of auditory hindbrain structures after completion of migration. Our results thus demonstrate that γ-crystallins can serve important extralenticular function as well.…”

Section: Discussionmentioning

confidence: 88%

Functional Role of γ-Crystallin N in the Auditory Hindbrain

et al. 2016

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γ-crystallins are major components of the vertebrate lens but show expression in other tissues as well. Their extralenticular functions remain so far unclear. Here, we explored such roles in the rodent superior olivary complex in which previous analysis demonstrated developmentally regulated expression of Crygd, Cryge and Crygn. Immunohistochemistry with novel antibodies against Crygd/e and Crygn indicate that expression of Crygd/e was moderate and varied between the perinatal superior olivary complex of mice, rats, and gerbils. Crygn-immunoreactivity was more robust and consistently highest in the medial nucleus of the trapezoid body, but also present in other nuclei of the superior olivary complex. To analyze the function of Crygn in the auditory hindbrain, we used a Crygn allele with a floxed exon 2. Upon pairing with Egr2::Cre mice, exon 2, encoding the first two greek key motifs of Crygn, was deleted in the developing auditory hindbrain. Anatomical analysis of these mice revealed a 20% volume reduction in the medial nucleus of the trapezoid body and a 7% reduction in the lateral superior olive at postnatal day 25. This was due to cell loss between postnatal days 4 and 25, whereas cell size was unaffected. Auditory brainstem responses showed normal threshold but a significant increase in the amplitude of wave IV. Crygn is hence required for postmigratory survival and proper function of auditory hindbrain neurons. These results ascertain for the first time an essential extralenticular role for γ-crystallins in vivo.

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En1 is necessary for survival of neurons in the ventral nuclei of the lateral lemniscus

Cited by 12 publications

References 47 publications

Nuclear derivatives and axonal projections originating from rhombomere 4 in the mouse hindbrain

Nuclear derivatives and axonal projections originating from rhombomere 4 in the mouse hindbrain

Glial Cell Expansion Coincides with Neural Circuit Formation in the Developing Auditory Brainstem

Functional Role of γ-Crystallin N in the Auditory Hindbrain

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