Ectoderm barcoding reveals neural and cochlear compartmentalization

Science, vol. 388, pp. 60–68

Abstract

Placodes and the neural crest are defining features of vertebrates. In this study, we investigate their lineages in mice using in utero approaches. We demonstrated that nanoinjection at embryonic day 7.5 targeted the ectoderm, including the future nervous system, placodes, and neural crest, allowing highly efficient manipulation of the future nervous system and inner ear. By using heritable DNA barcodes and high-throughput next-generation single-cell lineage tracing, we elucidated convergent differentiation pathways and identified distinct nervous system-, neural crest-, and otic placode-derived lineages. Clonal analyses identified early neural and cochlear compartmentalization, linking differentiated cell types to their progenitors or cellular siblings. This provides foundational insights for neuroscience and developmental biology.

Authors 9

1. Sandra de Haan corresponding Aachen Department of Human Genetics

   National Institutes of Health · Leiden University Medical Center · Karolinska Institutet · National Institute on Deafness and Other Communication Disorders

   Affiliation as printed

   Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden

   Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands

   Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA

2. Jingyan He corresponding

   Karolinska Institutet

   Affiliation as printed

   Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden

3. Agustín A. Corbat

   Karolinska Institutet

   Affiliation as printed

   Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden

4. Lenka Belicová

   Karolinska Institutet

   Affiliation as printed

   Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden

5. Michael Ratz

   Karolinska Institutet

   Affiliation as printed

   Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden

6. Elin Vinsland

   Karolinska Institutet

   Affiliation as printed

   Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden

7. Jonas Frisén

   Karolinska Institutet

   Affiliation as printed

   Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden

8. Matthew W. Kelley

   National Institutes of Health · National Institute on Deafness and Other Communication Disorders

   Affiliation as printed

   Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA

9. Emma Rachel Andersson corresponding

   Karolinska Institutet

   Affiliation as printed

   Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden