Most cited article - PubMed ID 37459514
Ancient vertebrate dermal armor evolved from trunk neural crest
The endostyle is an endodermal organ unique to nonvertebrate chordates except for lamprey larvae, where it serves as forerunner to the adult thyroid. Here, we examine whether the acquisition of neural crest in the vertebrate lineage played a role in the elaboration of the endostyle. CM-DiI lineage tracing reveals a neural crest contribution to the endostyle, and CRISPR-Cas9 mutagenesis of key neural crest genes causes endostyle defects including formation of a single rather than bilobed structure. RNA sequencing reveals gene profiles characteristic of embryonic neural crest cells and Schwann cell precursors in the developing endostyle. Contrasting with the prevailing view that the endostyle is an endoderm-derived organ, we propose that the acquisition of the neural crest played a critical step in promoting thyroid evolution from chordate endostyle.
Neurofibromatosis type 2 (NF-2) is a dominantly inherited genetic disorder that results from variants in the tumor suppressor gene, neurofibromin 2 (NF2). Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by inducible genetic knockout of nf2a/b, the zebrafish homologs of human NF2. Analysis of nf2a and nf2b expression revealed ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displayed lower expression levels. Induction of nf2a/b knockout at early stages increased the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggered the development of a spectrum of tumors, including vestibular Schwannomas, spinal Schwannomas, meningiomas and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.
- Keywords
- Cancer, Inducible knockout, Meninges, Neurofibromatosis type 2, Schwann cells, Zebrafish,
- MeSH
- Zebrafish * genetics embryology MeSH
- Animals, Genetically Modified MeSH
- Gene Knockout Techniques * MeSH
- Larva metabolism MeSH
- Humans MeSH
- Disease Models, Animal * MeSH
- Neurofibromatosis 2 genetics pathology metabolism MeSH
- Neurofibromatoses genetics pathology metabolism MeSH
- Neurofibromin 2 * genetics metabolism deficiency MeSH
- Cell Proliferation MeSH
- Zebrafish Proteins * genetics metabolism deficiency MeSH
- Schwann Cells metabolism pathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Neurofibromin 2 * MeSH
- Zebrafish Proteins * MeSH
In electroreceptive jawed vertebrates, embryonic lateral line placodes give rise to electrosensory ampullary organs as well as mechanosensory neuromasts. Previous reports of shared gene expression suggest that conserved mechanisms underlie electroreceptor and mechanosensory hair cell development and that electroreceptors evolved as a transcriptionally related "sister cell type" to hair cells. We previously identified only one transcription factor gene, Neurod4, as ampullary organ-restricted in the developing lateral line system of a chondrostean ray-finned fish, the Mississippi paddlefish (Polyodon spathula). The other 16 transcription factor genes we previously validated in paddlefish were expressed in both ampullary organs and neuromasts. Here, we used our published lateral line organ-enriched gene-set (arising from differential bulk RNA-seq in late-larval paddlefish), together with a candidate gene approach, to identify 25 transcription factor genes expressed in the developing lateral line system of a more experimentally tractable chondrostean, the sterlet (Acipenser ruthenus, a small sturgeon), and/or that of paddlefish. Thirteen are expressed in both ampullary organs and neuromasts, consistent with conservation of molecular mechanisms. Seven are electrosensory-restricted on the head (Irx5, Irx3, Insm1, Sp5, Satb2, Mafa and Rorc), and five are the first-reported mechanosensory-restricted transcription factor genes (Foxg1, Sox8, Isl1, Hmx2 and Rorb). However, as previously reported, Sox8 is expressed in ampullary organs as well as neuromasts in a catshark (Scyliorhinus canicula), suggesting the existence of lineage-specific differences between cartilaginous and ray-finned fishes. Overall, our results support the hypothesis that ampullary organs and neuromasts develop via largely conserved transcriptional mechanisms, and identify multiple transcription factors potentially involved in the formation of electrosensory versus mechanosensory lateral line organs.
- Keywords
- ampullary organ, electrosensory, lateral line organs, mechanosensory, neuromast, paddlefish, sterlet, sturgeon,
- Publication type
- Journal Article MeSH
Bone is an evolutionary novelty of vertebrates, likely to have first emerged as part of ancestral dermal armor that consisted of osteogenic and odontogenic components. Whether these early vertebrate structures arose from mesoderm or neural crest cells has been a matter of considerable debate. To examine the developmental origin of the bony part of the dermal armor, we have performed in vivo lineage tracing in the sterlet sturgeon, a representative of nonteleost ray-finned fish that has retained an extensive postcranial dermal skeleton. The results definitively show that sterlet trunk neural crest cells give rise to osteoblasts of the scutes. Transcriptional profiling further reveals neural crest gene signature in sterlet scutes as well as bichir scales. Finally, histological and microCT analyses of ray-finned fish dermal armor show that their scales and scutes are formed by bone, dentin, and hypermineralized covering tissues, in various combinations, that resemble those of the first armored vertebrates. Taken together, our results support a primitive skeletogenic role for the neural crest along the entire body axis, that was later progressively restricted to the cranial region during vertebrate evolution. Thus, the neural crest was a crucial evolutionary innovation driving the origin and diversification of dermal armor along the entire body axis.
- Keywords
- neural crest, scales, skeleton, sterlet sturgeon, vertebrate evolution,
- MeSH
- Biological Evolution MeSH
- Neural Crest * MeSH
- Skull MeSH
- Vertebrates * genetics MeSH
- Osteogenesis MeSH
- Fishes MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
