Postnatal shifts of interneuron position in the neocortex of normal and reeler mice: evidence for inward radial migration

doi:10.1016/j.neuroscience.2003.11.033

Neuroscience

Volume 124, Issue 3, 2004, Pages 605-618

https://doi.org/10.1016/j.neuroscience.2003.11.033 Get rights and content

Abstract

During development, interneurons migrate to precise positions in the cortex by tangential and radial migration. The objectives of this study were to characterize the net radial migrations of interneurons during the first postnatal week, and to investigate the role of reelin signaling in regulating those migrations. To observe radial migrations, we compared the laminar positions of interneurons (immunoreactive for GABA or Dlx) in mouse neocortex on postnatal days (P) 0.5 and P7.5. In addition, we used bromodeoxyuridine birthdating to reveal the migrations of different interneuron cohorts. To study the effects of reelin deficiency, experiments were performed in reeler mutant mice.

In normal P0.5 cortex, interneurons were most abundant in the marginal zone and layer 5. By P7.5, interneurons were least abundant in the marginal zone, and were distributed more evenly in the cortical plate. This change was attributed mainly to inward migration of middle- to late-born interneurons (produced on embryonic days (E) 13.5 to E16.5) from the marginal zone to layers 2–5. During the same interval, late-born projection neurons (non-immunoreactive for GABA or Dlx) migrated mainly outward, from the intermediate zone to upper cortical layers. In reeler cortex, middle- and late-born interneurons migrated from the superplate on P0.5, to the deep cortical plate on P7.5. Late-born projection neurons in reeler migrated in the opposite direction, from the intermediate zone to the deep cortical plate.

We conclude that many middle- and late-born interneurons migrate radially inward, from the marginal zone (or superplate) to the cortical plate, during the first postnatal week in normal and reeler mice. We propose that within the cortical plate, interneuron laminar positions may be determined in part by interactions with projection neurons born on the same day in neurogenesis.

Section snippets

Animals and genotyping

Mice were used according to a protocol approved by the Institutional Animal Care and Use Committee at the University of Washington, and in accordance with NIH guidelines. All efforts were made to minimize the number of mice used, as well as any pain or suffering. B6 Reln heterozygous mutant mice were purchased from Jackson Laboratories (Bar Harbor, ME, USA) and bred in a colony. Homozygous (−/−) mice were recognized phenotypically by ataxic behavior, abnormal cerebellar anatomy, and/or cortical

Changing distributions of interneurons in normal and reeler postnatal cortex

To label interneurons, antibodies against two markers were used: (1) GABA, which is expressed in migrating and mature interneurons; and (2) Dlx transcription factors (pan-Dlx antibody), which are expressed in interneurons and their precursors (Anderson et al., 1997, Eisenstat et al., 1999). GABA and Dlx were both used, to ensure that all stages of interneuron maturation were detected. To minimize potential variations of laminar fate due to gradients of cortical development (Caviness et al., 2000

Conclusions

Our results suggest that interneurons and projection neurons undergo distinct radial migrations during the first postnatal week (Fig. 10). It appears that middle- and late-born interneurons migrate both “inward” from the mz, and “outward” from the iz and vz/svz, to predetermined positions in the cortical plate. In contrast, late-born projection neurons migrate mainly outward from the iz. Despite their different migrations, the same cohorts of interneurons and projection neurons converge on

Discussion

We used cell birthdating and double labeling for interneuron markers (GABA and Dlx) to test the hypothesis that cortical interneurons migrate radially during the first postnatal week. Previous studies have found that interneurons can migrate both toward and away from the ventricle during embryonic life, but the magnitude and duration of inward migration have been uncertain (Nadarajah et al., 2002, Nadarajah et al., 2003, Polleux et al., 2002, Tanaka et al., 2003). Quite recently, studies by Ang

Acknowledgements

This work was supported by the National Institutes of Health (K08 NS01973), the Marian E. Smith Award, the Edward Mallinckrodt, Jr. Foundation (40^th Mallinckrodt Scholar), and the Shaw Professorship in Investigative Neuropathology to R.F.H.

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Postnatal shifts of interneuron position in the neocortex of normal and reeler mice: evidence for inward radial migration

Abstract

Section snippets

Animals and genotyping

Changing distributions of interneurons in normal and reeler postnatal cortex

Conclusions

Discussion

Acknowledgements

Dev Brain Res

Trends Neurosci

Neurobiol Dis

Prog Neurobiol

Neuron

Dev Brain Res

Trends Neurosci

Neuron

Neuroscience

Neuron

Neuron

Cell

Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse

J Neurosci

The subplate, a transient neocortical structureIts role in the development of connections between thalamus and cortex

Annu Rev Neurosci

Interneuron migration from basal forebrain to neocortexDependence on dlx genes

Science

Distinct cortical migrations from the medial and lateral ganglionic eminences

Development

Four-dimensional migratory coordinates of GABAergic interneurons in the developing mouse cortex

J Neurosci

Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse

Nature

Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex

Development

Neocortical malformation as consequence of nonadaptive regulation of neuronogenetic sequence

Ment Retard Dev Disab Res Rev

Emx1 is a marker for pyramidal neurons of the cerebral cortex

Cereb Cortex

A protein related to extracellular matrix proteins deleted in the mouse mutant reeler

Nature

Dynamics of cell migration from the lateral ganglionic eminence in the rat

J Neurosci

Cortical cells that migrate beyond area boundariesCharacterization of an early neuronal population in the lower intermediate zone of prenatal rats

Eur J Neurosci

DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation

J Comp Neurol

Times of generation of glutamic acid decarboxylase immunoreactive neurons in mouse somatosensory cortex

J Comp Neurol

Local differences in the amount of early cell death in neocortex predict adult local specializations

Science

Reelin is a detachment signal in tangential chain-migration during postnatal neurogenesis

Nat Neurosci

Disabled-1 functions cell autonomously during radial migration and cortical layering of pyramidal neurons

J Neurosci

In vitro analysis of the origin, migratory behavior, and maturation of cortical pyramidal cells

J Comp Neurol

Numbers and proportions of GABA-immunoreactive neurons in different areas of monkey cerebral cortex

J Neurosci

Beyond laminar fateToward a molecular classification of cortical projection/pyramidal neurons

Dev Neurosci

The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex

J Neurosci

The fates of cells generated at the end of neurogenesis in developing mouse cortex

J Neurobiol