Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb—a gene that is preferentially expressed by these cells—cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.
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Tomioka, N. et al. Neocortical origin and tangential migration of guidepost neurons in the lateral olfactory tract. J. Neurosci. 20, 5802–5812 (2000).
Shu, T., Li, Y., Keller, A. & Richards, L. J. The glial sling is a migratory population of developing neurons. Development 130, 2929–2937 (2003).
López-Bendito, G. et al. Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell 125, 127–142 (2006).
Niquille, M. et al. Transient neuronal populations are required to guide callosal axons: a role for semaphorin 3C. PLoS Biol. 7, e1000230 (2009).
Nikolaou, N. & Meyer, M. P. Lamination speeds the functional development of visual circuits. Neuron 88, 999–1013 (2015).
Tremblay, R., Lee, S. & Rudy, B. GABAergic interneurons in the neocortex: from cellular properties to circuits. Neuron 91, 260–292 (2016).
Zeisel, A. et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347, 1138–1142 (2015).
Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016).
Ascoli, G. A. et al. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat. Rev. Neurosci. 9, 557–568 (2008).
Klausberger, T. & Somogyi, P. Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321, 53–57 (2008).
Wonders, C. P. & Anderson, S. A. The origin and specification of cortical interneurons. Nat. Rev. Neurosci. 7, 687–696 (2006).
Kawaguchi, Y. & Kubota, Y. Physiological and morphological identification of somatostatin- or vasoactive intestinal polypeptide-containing cells among GABAergic cell subtypes in rat frontal cortex. J. Neurosci. 16, 2701–2715 (1996).
Wang, Y. et al. Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat. J. Physiol. (Lond.) 561, 65–90 (2004).
Xu, H., Jeong, H. Y., Tremblay, R. & Rudy, B. Neocortical somatostatin-expressing GABAergic interneurons disinhibit the thalamorecipient layer 4. Neuron 77, 155–167 (2013).
Gelman, D. M. & Marín, O. Generation of interneuron diversity in the mouse cerebral cortex. Eur. J. Neurosci. 31, 2136–2141 (2010).
Tanaka, D. H. & Nakajima, K. Migratory pathways of GABAergic interneurons when they enter the neocortex. Eur. J. Neurosci. 35, 1655–1660 (2012).
Tanaka, D. H., Oiwa, R., Sasaki, E. & Nakajima, K. Changes in cortical interneuron migration contribute to the evolution of the neocortex. Proc. Natl. Acad. Sci. USA 108, 8015–8020 (2011).
Wamsley, B. & Fishell, G. Genetic and activity-dependent mechanisms underlying interneuron diversity. Nat. Rev. Neurosci. 18, 299–309 (2017).
Miyoshi, G. & Fishell, G. GABAergic interneuron lineages selectively sort into specific cortical layers during early postnatal development. Cereb. Cortex 21, 845–852 (2011).
Villette, V. et al. Development of early-born γ-aminobutyric acid hub neurons in mouse hippocampus from embryogenesis to adulthood. J. Comp. Neurol. 524, 2440–2461 (2016).
Nowotschin, S. & Hadjantonakis, A. K. Use of KikGR a photoconvertible green-to-red fluorescent protein for cell labeling and lineage analysis in ES cells and mouse embryos. BMC Dev. Biol. 9, 49 (2009).
Marín, O., Valdeolmillos, M. & Moya, F. Neurons in motion: same principles for different shapes? Trends Neurosci. 29, 655–661 (2006).
Martini, F. J. et al. Biased selection of leading process branches mediates chemotaxis during tangential neuronal migration. Development 136, 41–50 (2009).
Hilscher, M. M., Leão, R. N., Edwards, S. J., Leão, K. E. & Kullander, K. Chrna2-Martinotti cells synchronize layer 5 type A pyramidal cells via rebound excitation. PLoS Biol. 15, e2001392 (2017).
Breunig, J. J. et al. Rapid genetic targeting of pial surface neural progenitors and immature neurons by neonatal electroporation. Neural Dev. 7, 26 (2012).
Xu, Q., Tam, M. & Anderson, S. A. Fate mapping Nkx2.1-lineage cells in the mouse telencephalon. J. Comp. Neurol. 506, 16–29 (2008).
Buchanan, K. A. et al. Target-specific expression of presynaptic NMDA receptors in neocortical microcircuits. Neuron 75, 451–466 (2012).
Bortone, D. S., Olsen, S. R. & Scanziani, M. Translaminar inhibitory cells recruited by layer 6 corticothalamic neurons suppress visual cortex. Neuron 82, 474–485 (2014).
Jacobson, C., Schnapp, B. & Banker, G. A. A change in the selective translocation of the Kinesin-1 motor domain marks the initial specification of the axon. Neuron 49, 797–804 (2006).
Xu, X., Roby, K. D. & Callaway, E. M. Mouse cortical inhibitory neuron type that coexpresses somatostatin and calretinin. J. Comp. Neurol. 499, 144–160 (2006).
Petreanu, L., Mao, T., Sternson, S. M. & Svoboda, K. The subcellular organization of neocortical excitatory connections. Nature 457, 1142–1145 (2009).
Ma, W. P. et al. Visual representations by cortical somatostatin inhibitory neurons–selective but with weak and delayed responses. J. Neurosci. 30, 14371–14379 (2010).
Cottam, J. C., Smith, S. L. & Häusser, M. Target-specific effects of somatostatin-expressing interneurons on neocortical visual processing. J. Neurosci. 33, 19567–19578 (2013).
Adesnik, H., Bruns, W., Taniguchi, H., Huang, Z. J. & Scanziani, M. A neural circuit for spatial summation in visual cortex. Nature 490, 226–231 (2012).
Jiang, X. et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science 350, aac9462 (2015).
Pfeffer, C. K., Xue, M., He, M., Huang, Z. J. & Scanziani, M. Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons. Nat. Neurosci. 16, 1068–1076 (2013).
Adesnik, H. Synaptic mechanisms of feature coding in the visual cortex of awake mice. Neuron 95, 1147–1159.e4 (2017).
Montijn, J. S., Vinck, M. & Pennartz, C. M. Population coding in mouse visual cortex: response reliability and dissociability of stimulus tuning and noise correlation. Front. Comput. Neurosci. 8, 58 (2014).
Marín, O. & Rubenstein, J. L. R. A long, remarkable journey: tangential migration in the telencephalon. Nat. Rev. Neurosci. 2, 780–790 (2001).
Marín, O., Yaron, A., Bagri, A., Tessier-Lavigne, M. & Rubenstein, J. L. Sorting of striatal and cortical interneurons regulated by semaphorin-neuropilin interactions. Science 293, 872–875 (2001).
Frazer, S. et al. Transcriptomic and anatomic parcellation of 5-HT3AR expressing cortical interneuron subtypes revealed by single-cell RNA sequencing. Nat. Commun. 8, 14219 (2017).
Tanaka, D. H., Maekawa, K., Yanagawa, Y., Obata, K. & Murakami, F. Multidirectional and multizonal tangential migration of GABAergic interneurons in the developing cerebral cortex. Development 133, 2167–2176 (2006).
Yokota, Y. et al. Radial glial dependent and independent dynamics of interneuronal migration in the developing cerebral cortex. PLoS One 2, e794 (2007).
Rakic, P. Neuron-glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electronmicroscopic study in Macacus Rhesus. J. Comp. Neurol. 141, 283–312 (1971).
de Frutos, C. A. et al. Reallocation of olfactory Cajal-Retzius cells shapes neocortex architecture. Neuron 92, 435–448 (2016).
Flames, N. et al. Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J. Neurosci. 27, 9682–9695 (2007).
Silberberg, S. N. et al. Subpallial enhancer transgenic lines: a data and tool resource to study transcriptional regulation of GABAergic cell fate. Neuron 92, 59–74 (2016).
De Marco García, N. V., Karayannis, T. & Fishell, G. Neuronal activity is required for the development of specific cortical interneuron subtypes. Nature 472, 351–355 (2011).
Mi, D. et al. Early emergence of cortical interneuron diversity in the mouse embryo. Science 360, 81–85 (2018).
Ma, Y., Hu, H., Berrebi, A. S., Mathers, P. H. & Agmon, A. Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice. J. Neurosci. 26, 5069–5082 (2006).
Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140 (2010).
Taniguchi, H. et al. A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71, 995–1013 (2011).
Batista-Brito, R., Close, J., Machold, R. & Fishell, G. The distinct temporal origins of olfactory bulb interneuron subtypes. J. Neurosci. 28, 3966–3975 (2008).
Sylwestrak, E. L. & Ghosh, A. Elfn1 regulates target-specific release probability at CA1-interneuron synapses. Science 338, 536–540 (2012).
López-Bendito, G. et al. Preferential origin and layer destination of GAD65-GFP cortical interneurons. Cereb. Cortex 14, 1122–1133 (2004).
Yu, W. M. et al. A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing. eLife 2, e01341 (2013).
Ng, D. et al. Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning. PLoS Biol. 7, e41 (2009).
Sousa, V. H., Miyoshi, G., Hjerling-Leffler, J., Karayannis, T. & Fishell, G. Characterization of Nkx6-2-derived neocortical interneuron lineages. Cereb. Cortex 19(Suppl 1), i1–i10 (2009).
Vong, L. et al. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71, 142–154 (2011).
Pla, R., Borrell, V., Flames, N. & Marín, O. Layer acquisition by cortical GABAergic interneurons is independent of Reelin signaling. J. Neurosci. 26, 6924–6934 (2006).
Englund, C. et al. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J. Neurosci. 25, 247–251 (2005).
Bentley, M., Decker, H., Luisi, J. & Banker, G. A novel assay reveals preferential binding between Rabs, kinesins, and specific endosomal subpopulations. J. Cell Biol. 208, 273–281 (2015).
Tashiro, A., Sandler, V. M., Toni, N., Zhao, C. & Gage, F. H. NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus. Nature 442, 929–933 (2006).
Pakan, J. M. et al. Behavioral-state modulation of inhibition is context-dependent and cell type specific in mouse visual cortex. eLife 5, e14985 (2016).
Williams, S. R. & Mitchell, S. J. Direct measurement of somatic voltage clamp errors in central neurons. Nat. Neurosci. 11, 790–798 (2008).
Kaifosh, P., Zaremba, J. D., Danielson, N. B. & Losonczy, A. SIMA: Python software for analysis of dynamic fluorescence imaging data. Front. Neuroinform. 8, 80 (2014).
Keemink, S. W. et al. FISSA: a neuropil decontamination toolbox for calcium imaging signals. Sci. Rep. 8, 3493 (2018).
We thank I. Andrews, A. Casillas, M. Fernández, and T. Gil for excellent technical assistance; F. Gage (Salk Institute for Biological Studies, CA, USA) and G. Banker (Oregon Health and Science University, OR, USA) for plasmids; L. Goodrich (MafbloxP/loxP, Harvard University, MA, USA), J. Huang (SstCre, Cold Spring Harbor Laboratory, NY, USA), and S. Arber (PvalbCre, Biozentrum and Friedrich Miescher Institute for Biomedical Research, Switzerland) for mouse colonies; and V. Jayaraman, R. Kerr, D. Kim, L. Looger, and K. Svoboda (GENIE Program and the Janelia Research Campus, VA, USA) for making GCaMP6 available. We are grateful to N. Dehorter, C. Houart, and M. Grubb for critical reading of the manuscript and to members of the Flames, Marín, and Rico laboratories for stimulating discussions and ideas. This work was supported by a grant from the European Research Council (ERC-2011-AdG 293683) to O.M., Marie Curie Actions of the European Union’s FP7 program (MC-CIG 631770) to N.R. and (IEF 624461) J.P., and funds from the Shirley Foundation, Patrick Wild Center, RS MacDonald Charitable Trust, and Simons Initiative for the Developing Brain to N.R. L.L. was the recipient of an EMBO long-term postdoctoral fellowship. N.R. is supported by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (102857/Z/13/Z).
The authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Integrated supplementary information
(a,c) Coronal sections through the somatosensory cortex of P30 Dlx1/2CreER;Ai9 (a) and Nkx2-1CreER;Ai9 (c) showing the distribution of TdTomato cells that also express PV or SST. Open arrowheads point to TdTomato-expressing cells that do not express PV (a’,a”) or SST (c’,c”), whereas arrowheads indicate TdTomato/PV (a’,a”) and TdTomato/SST (c’,c”) double-labeled cells, repeated with similar results over 3 animals. (b,d) Boxplots represent median, 1st and 3rd quartile, and 1.5 IQR for fraction of TdTomato/PV and TdTomato/SST double-labeled cells in Dlx1/2CreER;Ai9 (b) and Nkx2-1CreER;Ai9 (d) mice. n = 3 mice per genotype. Scale bar equals 100 µm.
(a) Schematic of experimental design for the imaging of Kikume Green-Red labeled interneurons. (b,c) Time-lapse images of Kikume Green-Red labeled interneurons immediately after photoconversion (b) and at the end of the experiment (c). The arrowhead indicates a cell migrating out of the MZ. Experiments were repeated over 10 different slices with similar results. (d) Cumulative frequency of migration speed for interneurons in the MZ (n = 48 cells). The dotted line represents the theoretical minimum speed required for migrating interneurons to leave the MZ during the experimental time (14 h). (e) Quantification of the fraction of cells at the MZ; n = 48 (theoretical), n = 141 (photo-converted) cells from 10 different slices; two-tailed Fisher's exact test, ***p < 0.001 (p = 7.03 e-8). (f) Schematic of experimental design for slice transplantation experiments. (g,h) Representative examples of slices following transplantation of MZ (g) and SVZ (h) derived interneurons. Asterisks indicate the original placement of transplanted cells. (i) Boxplots represent median, 1st and 3rd quartile, and 1.5 IQR for fraction of cells located in the MZ following transplantation of MZ and SVZ-derived interneurons. n = 10 and12 slices, from 5 and 6 animals for MZ and SVZ derived cells respectively; two-tailed Student t-test, **p < 0.01 (p = 4.545 e-5). Scale bars equal 100 µm (b,c) and 200 µm (g,h).
(a) Schematic of experimental design for the isolation of neurons in progressively deeper positions of the embryonic cortex. (b) Boxplots represent median, 1st and 3rd quartile, and 1.5 IQR for percentage of TdTomato (CR + cells) and Tbr2 + cells in each fraction, normalized to total cell number, n = 3 litters of embryos. (c–g) Representative images showing TdTomato (CR + cells) and Tbr2 + cells in the different cellular fractions after dissociation and plating. Fraction 1 is closest to the pial surface and fraction 5 is closest to the ventricular zone (VZ). Experiments were repeated 3 times with similar results. Scale bar equals 200 µm.
(a) Coronal sections through the cortex of E17.5 from SstCre;Ai9 mice showing expression of MafB (a and a”) in migrating SST + interneurons (a’ and a”), repeated over 3 animals with similar results (b) Quantification of mean fluorescence intensity for MafB in SST + /tdTomato + cells migrating through the MZ or IZ/SVZ; n = 3 mice; one-way ANOVA; ***p < 0.001 (p = 0.0004 for MafB) and p = 0.82 (tdTomato). Histograms represent mean ± s. e. m. Scale bar equals 100 µm.
(a) Heatmap representing relative levels (z-scores) of genes differentially enriched in SST + cells migrating through the SVZ at E17.5, with FDR set at < 5% using the Benjamini-Hochberg method. (b) Heatmap representing relative levels (z-scores) of SVZ-enriched genes (from a) in different classes of SST + interneurons from the adult visual cortex (data from Ref. 8). (c) Heatmap representing relative levels (z-scores) of genes expressed in different classes of SST + interneurons from the adult visual cortex (data from Ref. 8). Chrna2 appears to be preferentially expressed in Cdk6 + and Myh8 + populations of SST + cells.
(a) Schematic of experimental design for target injection in the MZ at birth. (b–e) Coronal sections through the telencephalon at P0 showing the extent of the distribution of Fluosphere Alexa 488 beads 1 h after injection, repeated 3 times with similar results (f) Schematic of experimental design for pial surface electroporation. (g) Coronal sections through the telencephalon 24 h after electroporation, repeated in 6 animals similar results. (h) Schematic of experimental design for pial surface electroporation. (i,j) Coronal sections through the telencephalon 16 h after electroporation, repeated over 5 animals with similar results. CP, cortical plate; CPu, caudoputamen nucleus; MZ, marginal zone; PCx, piriform cortex; V and VI, layers 5 and 6. Scale bars equal 200 µm (b–e) and 100 µm (g,i,j).
(a) Schematic of experimental design for pial surface electroporation in Cre-expressing neonates. (b) Coronal section through the cortex at P21 following pial surface electroporation at birth. (c) Quantification of the laminar distribution of SST + interneurons at P21 following pial surface electroporation at birth, n = 106 cells from 15 animals. Error bars represent binomial proportion confidence interval. (d) Morphological description of surface electroporated cells. Scale bar equal 200 µm.
Supplementary Figure 8 Normal distribution of SST+ migrating interneurons in Neto1 and Elfn1 mutants.
(a,b,d,e) Coronal sections through the cortex of E16.5 SstCre;Neto1+/-;RCE (a), SstCre;Neto1-/-;RCE (b), SstCre;Elfn1+/-;RCE (d), and SstCre;Elfn1-/-;RCE (e) mouse embryos, repeated over 3 mice per conditions with similar results. (c,f) Boxplots represent median, 1st and 3rd quartile, and 1.5 IQR for fraction of SST + cells in the MZ; n = 11 sections per mice, 3 mice for each genotype; one-way ANOVA, p = 0.114 and p = 0.614, respectively. CP, cortical plate; MZ, marginal zone; SP, subplate; V and VI. Scale bar equals 100 µm.
Supplementary Figure 9 Non-Martinotti SST+ cells have normal axonal length in conditional Mafb mutant mice.
(a) Schematic of experimental design for the labeling of interneuron progenitor cells using conditional retroviruses in Cre-expressing embryos. (b) Boxplots represent median, 1st and 3rd quartile, and 1.5 IQR for axonal length in non-Martinotti SST + interneurons in layer 2/3, n = 23 and 17 cells from 8 and 10 mice of control and mutant genotype, respectively. Two-tailed Student t-test, p = 0.87. (c,d) Representative images of SST + interneurons at P21 obtained through viral labeling at E14.5, repeated with similar results in 8 and 10 mice respectively. Scale bar equals 100 µm.
(a–c) Coronal sections through the somatosensory cortex of P21 SstCre;Mafb+/+;RCE (a, d), SstCre;Mafbfl/+;RCE (b, e), and SstCre;Mafbfl/fl;RCE (c, f) mice showing expression of Calretinin (CR, a–c) and Calbindin (CB, d–f) in SST + interneurons (GFP). (g, h) Quantification of the laminar distribution of SST + /CR + (g) and SST/CB + (h) cells for each genotype; n = 10 sections per animal, 3 mice per genotype; two-way ANOVA with post-hoc by Tukey HSD; p = 0.681 and p = 0.735 for CR and CB, respectively. Scale bar equals 100 µm.
(a) Representative traces of voltage response to a depolarizing 150 pA current injection in layer 2/3 Martinotti cells from P21-28 SstCre;Mafbfl/+;RCE and SstCre;Mafbfl/fl;RCE mice. (b) Table showing intrinsic properties of layer 2/3 Martinotti cells from P21-28 SstCre;Mafbfl/+;RCE and SstCre;Mafbfl/fl;RCE mice. p-values calculated by two-tailed Mann-Whitney U test. Bar graph represents mean ± s.e.m., n = 22 and 16 cells, from 10 Mafbfl/+;RCE and10 SstCre;Mafbfl/fl;RCE mice, respectively. (c-g) Quantification of resting membrane potential (c), input resistance (d), action potential threshold (e), rheobase (f) and action potential half width (g). for (c-g), Bar graph represents mean ± s.e.m., n = 22 and 16 cells, from 10 Mafbfl/+;RCE and10 SstCre;Mafbfl/fl;RCE mice, respectively. (h) Number of action potentials evoked in response to increasing current injections in layer 2/3 Martinotti cells from P21-28 SstCre;Mafbfl/+;RCE and SstCre;Mafbfl/fl;RCE mice. Data is presented as mean ± s.e.m., n = 22 and 16 cells, from 10 MafBfl/+;RCE and10 SstCre;Mafbfl/fl;RCE mice, respectively (i) Bar graph represents mean ± s.e.m. of maximum action potential frequency evoked in layer 2/3 Martinotti cells from P21-28,n = 22 and 16 cells, from 10 Mafbfl/+;RCE and10 SstCre;Mafbfl/fl;RCE mice, respectively; two-tailed Student's T-test p = 0.30. (j) Fraction of the maximal response recorded from individual layer 2/3 pyramidal neurons following stimulation of ChR2-expressing SST + cells in SstCre;Mafbfl/+;RCE and SstCre;Mafbfl/fl;RCE mice at increasing LED intensities. Data is presented as mean ± s.e.m., n = 19 and 12 cells 6 SstCre;Mafbfl/+;RCE and 7 SstCre;Mafbfl/fl;RCE mice, respectively. (k) Bar graph represents mean ± s.e.m. for of the minimal LED intensity required to evoke a detectable input in layer 2/3 pyramidal neurons from SST + cells expressing ChR2, n = 19 and 12 cells from 6 SstCre;Mafbfl/+;RCE and 7 SstCre;Mafbfl/fl;RCE mice, respectively. Two-tailed Student's T-test, p = 0.39. RMP, resting membrane potential; Capacitance, membrane capacitance; IR, input resistance; Sag, h-current sag; AP Threshold, action potential threshold; Amplitude, action potential amplitude; Rise time, action potential rise time; Decay time, action potential decay time; Half width, action potential half width; fAHP, fast after-hyperpolarization amplitude; Delay, delay to first action potential.
Supplementary Figures 1–11
Summary of data and statistical analyses for Figures 1, 2, 3, 4, 5, 6, and 7 and Supplementary Figures 2, 3, 4, 7, 8, 9, 10, and 11
Supplementary Video 1 – Photoconversion and tracking of interneurons migrating through the MZ (related to Supplementary Figure 2).
Time-lapse movie showing maximum projections of interneurons photoconverted from Kikume Green to Red over 14 hours in E14.5 Nkx2-1-Cre slices electroporated with conditionally expressing Kikume. Images were taken every 2 hours with covering a z-interval of 80 μm. Experiments were repeated 10 times on independent slices with similar results.
Supplementary Video 2 – Putative SST+ interneurons leave a trailing process behind when they migrate into the cortical plate (related to Figure 4a).
Time-lapse imaging showing maximum projections of migrating interneurons from the MZ into the cortical plate in slices from Dlx1/2CreER;Ai9 embryos. Images were taken for 60 hours every 2 hours covering a z-interval of 40 μm. For each frame, track lines represent the trajectory of the cell soma (blue) and the tip of the neural process (red) closest to the marginal zone (MZ). Time-lapse were repeated with similar results for n = 11 cells from 8 animals.
Supplementary Video 3 – Migration of putative PV+ interneurons from the MZ into the cortical plate (related to Figure 4b).
Time-lapse imaging showing maximum projections of migrating interneuron from the MZ into the cortical plate in slices from Nkx2-1CreER;Ai9 embryos. Images were taken for 60 hours every 2 hours covering a z-interval of 40 μm. For each frame, track lines represent the trajectory of the cell soma (blue) and the tip of the neural process (red) closest to the marginal zone (MZ). Time-lapse were repeated with similar results for n = 8 cells from 5 animals.
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Lim, L., Pakan, J.M.P., Selten, M.M. et al. Optimization of interneuron function by direct coupling of cell migration and axonal targeting. Nat Neurosci 21, 920–931 (2018) doi:10.1038/s41593-018-0162-9
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