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Dev Dyn
2006 Dec 01;23512:3199-212. doi: 10.1002/dvdy.20959.
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The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish.
Montero-Balaguer M
,
Lang MR
,
Sachdev SW
,
Knappmeyer C
,
Stewart RA
,
De La Guardia A
,
Hatzopoulos AK
,
Knapik EW
.
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The zebrafish mutation mother superior (mosm188) leads to a depletion of neural crest (NC) derivatives including the craniofacial cartilageskeleton, the peripheral nervous system (sympathetic neurons, dorsal root ganglia, enteric neurons), and pigment cells. The loss of derivatives is preceded by a reduction in NC-expressed transcription factors, snail1b, sox9b, sox10, and a specific loss of foxd3 expression in NC progenitor cells. We employed genetic linkage analysis and physical mapping to place the mosm188 mutation on zebrafish chromosome 6 in the vicinity of the foxd3 gene. Furthermore, we found that mosm188 does not complement the sym1/foxd3 mutation, indicating that mosm188 resides within the foxd3 locus. Injection of PAC clones containing the foxd3 gene into mosm188 embryos restored foxd3 expression in NC progenitors and suppressed the mosm188 phenotype. However, sequencing the foxd3 transcribed area in mosm188 embryos did not reveal nucleotide changes segregating with the mosm188 phenotype, implying that the mutation most likely resides outside the foxd3-coding region. Based on these findings, we propose that the mosm188 mutation perturbs a NC-specific foxd3 regulatory element. Further analysis of mosm188 mutants and foxd3 morphants revealed that NC cells are initially formed, suggesting that foxd3 function is required to maintain the pool of NC progenitors.
Figure 2. The mosm188 mutation affects migratory cranial neural crest. A,B:dlx8 expression was analyzed by in situ hybridization at 36 hpf in the craniofacial primordia of wild-type (A) and mosm188 (B) embryos. In mosm188mutants, expression appears slightly reduced in the first primordium but it is faint in the second (arrow in all panels) and absent in the posterior streams. C,D: Dorsal view of dlx2 expression at 24 hpf shows markedly reduced expression in the first two neural crest streams and almost complete absence in the postotic ones. E,F: Expression of the paraxial mesoderm and headmesenchyme marker wnt5a is substantially reduced at 24 hpf in the second and posterior NC streams in the mosm188 mutants while the first arch expression appears unaffected. G,H: The expression of sox9a, a marker of cranial mesenchymal condensations, is reduced in the first arch and is completely abolished in the second and posterior arches (24 hpf). I-L: The hox gene expression in hindbrainrhombomeres (r) is comparable between wild-type (I, K) and mosm188 (J, L) embryos, but expression of hoxa2 in the hyoid neural crest stream is largely absent, (arrow, J). Expression of hoxa2 and hoxb3 in the postotic stream is considerably reduced (white arrowhead in I,L).
Figure 4. Pigment cell progenitors show deficits in the mosm188 mutants. Expression analysis of pigment specific genes in wild type (A, C, E, G) lateral and (A', C', E', G') dorsal views, and in mosm188 mutants (B, D, F, H) lateral and (B', D', F', H') dorsal views as revealed by whole mount in situ hybridization in 22 hpf embryos. A-B': Expression of mitfa/nac, the early marker of pigment progenitors, is significantly downregulated in the trunk region while the mid-hindbrain boundary domain is unaffected in mosm188 mutants. C-D': Similarly, the melanophores specific dct/trp2 expression is largely absent in mosm188 mutants at this stage. E-F':Fms that specifies melanophore and xanthophore lineages is essentially absent in mosm188mutants as is xanthine dehydrogenase (G-H'), the enzyme in pteridine synthesis pathway that marks lineage-committed xanthoblasts.
Figure 6. Expression of NC specification genes. A,B: Expression of snail1b in the premigratory NC cells (arrow) of wild-type embryos (A) is localized to the dorso-lateral edge of the neural tube, but it is greatly reduced in mosm188 mutants (B). The expression in the somites is unaltered. The arrowheads in wild-type embryos demarcate the position of the otic vesicle. C,D:Expression of sox9b is greatly reduced in NC progenitors (arrows) in mosm188 mutants (D), while the otic vesicle expression (arrowheads) is unaltered. E,F: Expression of sox10 in premigratory NC cells of wild-type embryos (E) is localized to the dorso-lateral edge of the neural tube (arrow). Sox10 expression is greatly reduced in mosm188 mutants (F), while the otic vesicle expression (arrowheads) is unaltered. G,H: The wild-type pattern (G) of crestin expression in the cranial region is absent in mosm188 mutants (H), but it is only reduced in the trunk. Lateral views in A-F and dorsal flat mounts in G and H, anterior to the left.
