neural crest Dotaz Zobrazit nápovědu
Developmental and cell biology series ; 36
2nd ed. xxiii, 445 s. : il.
- MeSH
- crista neuralis MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biologie
- neurologie
1st ed. 273 s., obr.
- MeSH
- crista neuralis MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- neurologie
[1st ed.] x, 313 s. : il.
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
- crista neuralis embryologie růst a vývoj MeSH
- keratiny analýza diagnostické užití MeSH
- Merkelovy buňky cytologie MeSH
- Publikační typ
- kongresy 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
- chrupavka abnormality embryologie MeSH
- crista neuralis embryologie metabolismus MeSH
- forkhead transkripční faktory biosyntéza genetika MeSH
- hlavové nervy embryologie MeSH
- homeodoménové proteiny genetika MeSH
- krvácení genetika MeSH
- lebka embryologie inervace MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- represorové proteiny biosyntéza genetika MeSH
- srdce embryologie MeSH
- transkripční faktor SOX9 biosyntéza genetika MeSH
- vrozené srdeční vady embryologie genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
