Developmental and cell biology series ; 36
2nd ed. xxiii, 445 s. : il.
- MeSH
- Neural Crest MeSH
- Conspectus
- Biochemie. Molekulární biologie. Biofyzika
- NML Fields
- biologie
- neurologie
1st ed. 273 s., obr.
- MeSH
- Neural Crest MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- neurologie
[1st ed.] x, 313 s. : il.
- Conspectus
- Anatomie člověka a srovnávací anatomie
- NML Fields
- neurovědy
- embryologie a teratologie
Schwann cell precursors (SCPs) are nerve-associated progenitors that can generate myelinating and non-myelinating Schwann cells but also are multipotent like the neural crest cells from which they originate. SCPs are omnipresent along outgrowing peripheral nerves throughout the body of vertebrate embryos. By using single-cell transcriptomics to generate a gene expression atlas of the entire neural crest lineage, we show that early SCPs and late migratory crest cells have similar transcriptional profiles characterised by a multipotent "hub" state containing cells biased towards traditional neural crest fates. SCPs keep diverging from the neural crest after being primed towards terminal Schwann cells and other fates, with different subtypes residing in distinct anatomical locations. Functional experiments using CRISPR-Cas9 loss-of-function further show that knockout of the common "hub" gene Sox8 causes defects in neural crest-derived cells along peripheral nerves by facilitating differentiation of SCPs towards sympathoadrenal fates. Finally, specific tumour populations found in melanoma, neurofibroma and neuroblastoma map to different stages of SCP/Schwann cell development. Overall, SCPs resemble migrating neural crest cells that maintain multipotency and become transcriptionally primed towards distinct lineages.
- MeSH
- Ambystoma anatomy & histology embryology MeSH
- Neural Crest anatomy & histology embryology MeSH
- Pharynx anatomy & histology embryology MeSH
- Publication type
- Congress MeSH
- MeSH
- Neural Crest embryology growth & development MeSH
- Keratins analysis diagnostic use MeSH
- Merkel Cells cytology MeSH
- Publication type
- Congress MeSH
BACKGROUND: TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. RESULTS: We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. CONCLUSIONS: Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.
- MeSH
- Cartilage abnormalities embryology MeSH
- Neural Crest embryology metabolism MeSH
- Forkhead Transcription Factors biosynthesis genetics MeSH
- Cranial Nerves embryology MeSH
- Homeodomain Proteins genetics MeSH
- Hemorrhage genetics MeSH
- Skull embryology innervation MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Repressor Proteins biosynthesis genetics MeSH
- Heart embryology MeSH
- SOX9 Transcription Factor biosynthesis genetics MeSH
- Heart Defects, Congenital embryology genetics MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
