Stereological study of postnatal development in the mouse utricular macula

Kirkegaard, Mette; Nyengaard, Jens Randel

doi:10.1002/cne.20736

Cited by 30 publications

(36 citation statements)

References 44 publications

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“…Those reports attributed the statistical increases to postnatal hair cell differentiation and the direct conversion of supporting cells into hair cells (Rusch et al 1998;Kirkegaard and Nyengaard 2005). However, we suspected that previously undetected populations of postnatally dividing progenitors might continue to produce progeny that would become new hair cells, thus contributing to the growth of the utricle's sensory epithelium.…”

Section: Introductionmentioning

confidence: 78%

“…Interpretation of those limited data appeared to lead to the conclusion that little or no mitotic production of hair cells occurs in mice after birth (Rusch et al 1998;Kirkegaard and Nyengaard 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with this, early investigations in rodents reported that the production of hair cells and supporting cells peaks during the second half of embryogenesis and declines precipitously before birth (Ruben 1967; Sans and Chat 1982; Lee et al 2006). Yet, recent statistical density estimates have suggested that hair cell numbers in mouse utricles continue to increase in the weeks after birth (Rusch et al 1998;Kirkegaard and Nyengaard 2005).…”

Section: Introductionmentioning

confidence: 99%

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Over Half the Hair Cells in the Mouse Utricle First Appear After Birth, with Significant Numbers Originating from Early Postnatal Mitotic Production in Peripheral and Striolar Growth Zones

Burns

Baker

et al. 2012

JARO

124

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Many non-mammalian vertebrates produce hair cells throughout life and recover from hearing and balance deficits through regeneration. In contrast, embryonic production of hair cells declines sharply in mammals where deficits from hair cell losses are typically permanent. Hair cell density estimates recently suggested that the vestibular organs of mice continue to add hair cells after birth, so we undertook comprehensive counting in murine utricles at different ages. The counts show that 51 % of the hair cells in adults arise during the 2 weeks after birth. Immature hair cells are most common near the neonatal macula's peripheral edge and striola, where anti-Ki-67 labels cycling nuclei in zones that appear to contain niches for supporting-cell-like stem cells. In vivo lineage tracing in a novel reporter mouse where tamoxifen-inducible supporting cell-specific Cre expression switched tdTomato fluorescence to eGFP fluorescence showed that proteolipid-protein-1-expressing supporting cells are an important source of the new hair cells. To assess the contributions of postnatal cell divisions, we gave mice an injection of BrdU or EdU on the day of birth. The labels were restricted to supporting cells 1 day later, but by 12 days, 31 % of the labeled nuclei were in myosin-VIIA-positive hair cells. Thus, hair cell populations in neonatal mouse utricles grow appreciably through two processes: the progressive differentiation of cells generated before birth and the differentiation of new cells arising from divisions of progenitors that progress through S phase soon after birth. Subsequent declines in these processes coincide with maturational changes that appear unique to mammalian supporting cells.

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Section: Introductionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Over Half the Hair Cells in the Mouse Utricle First Appear After Birth, with Significant Numbers Originating from Early Postnatal Mitotic Production in Peripheral and Striolar Growth Zones

Burns

Baker

et al. 2012

JARO

124

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“…The increase in Kir2.1 mRNA expression during the 1st postnatal wk also coincided with the continued maturation of the vestibular system in mice (Rüsch et al 1998). Furthermore, the total number of mature hair cells continues to increase until P16 (Kirkegaard and Nyengaard 2005;Li et al 2008), which may contribute to the higher Kir2.1 mRNA expression level measured at P25 compared with P7.…”

Section: Inward Rectifier Currents In Utricle Hair Cellsmentioning

confidence: 87%

“…None of the other Kir2 family subunits displayed substantial expression at the developmental onset of I K1 or at any time point that we examined. Furthermore, Kirkegaard and Nyengaard (2005) found that hair cell numbers in mouse vestibular epithelia increase until P16. A larger number of hair cells expressing Kir2.1 are consistent with our data, which show an increase in Kir2.1 mRNA expression between P7 and P25.…”

Section: Kir2mentioning

confidence: 99%

The function and molecular identity of inward rectifier channels in vestibular hair cells of the mouse inner ear

Levin

Holt

2012

Journal of Neurophysiology

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Inner ear hair cells respond to mechanical stimuli with graded receptor potentials. These graded responses are modulated by a host of voltage-dependent currents that flow across the basolateral membrane. Here, we examine the molecular identity and the function of a class of voltage-dependent ion channels that carries the potassium-selective inward rectifier current known as IK1. IK1has been identified in vestibular hair cells of various species, but its molecular composition and functional contributions remain obscure. We used quantitative RT-PCR to show that the inward rectifier gene, Kir2.1, is highly expressed in mouse utricle between embryonic day 15 and adulthood. We confirmed Kir2.1 protein expression in hair cells by immunolocalization. To examine the molecular composition of IK1, we recorded voltage-dependent currents from type II hair cells in response to 50-ms steps from −124 to −54 in 10-mV increments. Wild-type cells had rapidly activating inward currents with reversal potentials close to the K+equilibrium potential and a whole-cell conductance of 4.8 ± 1.5 nS ( n = 46). In utricle hair cells from Kir2.1-deficient (Kir2.1−/−) mice, IK1was absent at all stages examined. To identify the functional contribution of Kir2.1, we recorded membrane responses in current-clamp mode. Hair cells from Kir2.1−/−mice had significantly ( P < 0.001) more depolarized resting potentials and larger, slower membrane responses than those of wild-type cells. These data suggest that Kir2.1 is required for IK1in type II utricle hair cells and contributes to hyperpolarized resting potentials and fast, small amplitude receptor potentials in response to current inputs, such as those evoked by hair bundle deflections.

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Specializations of intercellular junctions are associated with the presence and absence of hair cell regeneration in ears from six vertebrate classes

Burns

Collado

Oliver

et al. 2013

J of Comparative Neurology

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Sensory hair cell losses lead to hearing and balance deficits that are permanent for mammals, but temporary for nonmammals because supporting cells in their ears give rise to replacement hair cells. In mice and humans, vestibular supporting cells grow exceptionally large circumferential F-actin belts and their junctions express E-cadherin in patterns that strongly correlate with postnatal declines in regeneration capacity. In contrast, chicken supporting cells retain thin F-actin belts throughout life and express little E-cadherin. To determine whether the junctions in chicken ears might be representative of other ears that also regenerate hair cells, we investigated inner ears from dogfish sharks, zebrafish, bullfrogs, Xenopus, turtles, and the lizard, Anolis. As in chickens, the supporting cells in adult zebrafish, Xenopus, and turtle ears retained thin circumferential F-actin belts and expressed little E-cadherin. Supporting cells in adult sharks and bullfrogs also retained thin belts, but were not tested for E-cadherin. Supporting cells in adult Anolis exhibited wide, but porous webs of F-actin and strong E-cadherin expression. Anolis supporting cells also showed some cell cycle reentry when cultured. The results reveal that the association between thin F-actin belts and low E-cadherin is shared by supporting cells in anamniotes, turtles, and birds, which all can regenerate hair cells. Divergent junctional specializations in supporting cells appear to have arisen independently in Anolis and mammals. The presence of webs of F-actin at the junctions in Anolis appears compatible with supporting cell proliferation, but the solid reinforcement of the F-actin belts in mammals is associated with its absence.

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Stereological study of postnatal development in the mouse utricular macula

Cited by 30 publications

References 44 publications

Over Half the Hair Cells in the Mouse Utricle First Appear After Birth, with Significant Numbers Originating from Early Postnatal Mitotic Production in Peripheral and Striolar Growth Zones

Over Half the Hair Cells in the Mouse Utricle First Appear After Birth, with Significant Numbers Originating from Early Postnatal Mitotic Production in Peripheral and Striolar Growth Zones

The function and molecular identity of inward rectifier channels in vestibular hair cells of the mouse inner ear

Specializations of intercellular junctions are associated with the presence and absence of hair cell regeneration in ears from six vertebrate classes

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