Effects of Melanocyte-Stimulating Hormone on Wild-Type and White Axolotl Neural Crest Cells

1995 ◽  
Vol 210 (2) ◽  
pp. 239-245
Author(s):  
A.D. Dean ◽  
S.K. Frostmason
Keyword(s):  
Neural Crest ◽  
Neural Crest Cells ◽  
Wild Type ◽  
Melanocyte Stimulating Hormone ◽  
Stimulating Hormone

The chinless mutation and neural crest cell interactions in zebrafish jaw development

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1417-1426 ◽  
Author(s):  
T.F. Schilling ◽  
C. Walker ◽  
C.B. Kimmel
Keyword(s):  
Neural Crest ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Paraxial Mesoderm ◽  
Wild Type ◽  
Host Genotype ◽  
Pharyngeal Arches ◽  
Expression Studies ◽  
Gene Expression Studies ◽  
Cranial Neural Crest Cells

During vertebrate development, neural crest cells are thought to pattern many aspects of head organization, including the segmented skeleton and musculature of the jaw and gills. Here we describe mutations at the gene chinless, chn, that disrupt the skeletal fates of neural crest cells in the head of the zebrafish and their interactions with muscle precursors. chn mutants lack neural-crest-derived cartilage and mesoderm-derived muscles in all seven pharyngeal arches. Fate mapping and gene expression studies demonstrate the presence of both undifferentiated cartilage and muscle precursors in mutants. However, chn blocks differentiation directly in neural crest, and not in mesoderm, as revealed by mosaic analyses. Neural crest cells taken from wild-type donor embryos can form cartilage when transplanted into chn mutant hosts and rescue some of the patterning defects of mutant pharyngeal arches. In these cases, cartilage only forms if neural crest is transplanted at least one hour before its migration, suggesting that interactions occur transiently in early jaw precursors. In contrast, transplanted cells in paraxial mesoderm behave according to the host genotype; mutant cells form jaw muscles in a wild-type environment. These results suggest that chn is required for the development of pharyngeal cartilages from cranial neural crest cells and subsequent crest signals that pattern mesodermally derived myocytes.

scholarly journals Noncoding microdeletion in mouse Hgf disrupts neural crest migration into the stria vascularis, reduces the endocochlear potential and suggests the neuropathology for human nonsyndromic deafness DFNB39

2019 ◽  
Author(s):  
Robert J. Morell ◽  
Rafal Olszewski ◽  
Risa Tona ◽  
Samuel Leitess ◽  
Julie M. Schultz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Neural Crest ◽  
Inner Ear ◽  
Stria Vascularis ◽  
Ion Homeostasis ◽  
Neural Crest Cells ◽  
Endocochlear Potential ◽  
Wild Type ◽  
Nonsyndromic Deafness ◽  
Hepatocyte Growth

AbstractHepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mouse, a deficiency of HGF expression limited to the auditory system, or over-expression of HGF, cause neurosensory deafness. In human, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39. However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10bp deletion (del10) in Hgf, which is located in the 3’UTR of a conserved short isoform (Hgf/NK0.5). Mice homozygous for del10 exhibit moderate-to-profound hearing loss at four weeks of age as measured by pure-tone auditory brainstem responses (ABRs). The wild type +80 millivolt endocochlear potential (EP) was significantly reduced in homozygous del10 mice compared to wild type littermates. In normal cochlea, EPs are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to dysfunctional ion homeostasis in the SV and a loss of EP, recapitulating human DFNB39 deafness.Significance StatementHereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously we reported that human deafness DFNB39 is associated with noncoding variants in the 3’UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fined-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 base pair deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic.

Agouti-Related Maturation and Tissue Distribution of oc-Melanocyte Stimulating Hormone in Wild-Type (AwJ/AwJ) and Mutant (Ay/a, a/a) Mice

1998 ◽  
Vol 11 (5) ◽  
pp. 310-313
Author(s):  
DAVID G. MONROE ◽  
LOREN P. WIPE ◽  
MAUREEN R. DIGGINS ◽  
DUANE P. MATTHEES ◽  
NELS H. GRANHOLM
Keyword(s):  
Tissue Distribution ◽  
Wild Type ◽  
Melanocyte Stimulating Hormone ◽  
Stimulating Hormone

Early Death of Neural Crest Cells is Responsible for Total Enteric Aganglionosis in Sox10Dom/Sox10Dom Mouse Embryos

1999 ◽  
Vol 2 (6) ◽  
pp. 559-569 ◽  
Author(s):  
Raj P. Kapur
Keyword(s):  
Neural Crest ◽  
Neural Crest Cell ◽  
Hirschsprung Disease ◽  
Early Death ◽  
Neural Crest Cells ◽  
Wild Type ◽  
Crest Cell ◽  
Insight Into ◽  
Intestinal Aganglionosis ◽  
Migratory Pathway

Intestinal aganglionosis results from homologous genetic defects in humans and mice, including mutations of Sox10, which encodes a transcription factor expressed in neural crest cells. To gain insight into the embryological basis for this condition, the phenotype and pathogenesis of intestinal aganglionosis in Sox10 Dom/ Sox10 Dom embryos were studied. The distribution of enteric neural precursors and other neural crest derivatives in Sox10 Dom/ Sox10 Dom embryos was analyzed with immunochemical and transgenic markers. The ability of wild-type neural crest cells to colonize Sox10 Dom/ Sox10 Dom intestinal ex-plants was evaluated by appositional grafts under the renal capsule. Apoptosis was studied by TUNEL labeling. Sox10 Dom/ Sox10 Dom embryos died pre- or perinatally with total enteric aganglionosis and hypoplasia or agenesis of nonenteric ganglia. Mutant crest cells failed to colonize any portion of the Sox10 Dom/ Sox10 Dom gut, but wild-type neural crest cells were able to colonize explanted segments of Sox10 Dom/ Sox10 Dom embryonic intestine. In Sox10 Dom/ Sox10 Dom embryos, apoptosis was increased in sites of early neural crest cell development, before these cells enter the gut. Sox10 Dom/ Sox10 Dom embryos are one of many genetic animal models for human Hirschsprung disease. The underlying problem is probably not the enteric microenvironment, since Sox10 Dom/ Sox10 Dom intestine supports colonization and neuronal differentiation by wild-type neural crest cells. Instead, excessive cell death occurs in mutant neural crest cells early in their migratory pathway. Comparison with other models suggests that genetic heterogeneity of aganglionosis correlates with different pathogenetic mechanisms.

scholarly journals The melanocortin 1 receptor is the principal mediator of the effects of agouti signaling protein on mammalian melanocytes

2001 ◽  
Vol 114 (5) ◽  
pp. 1019-1024 ◽  
Author(s):  
Z.A. Abdel-Malek ◽  
M.C. Scott ◽  
M. Furumura ◽  
M.L. Lamoreux ◽  
M. Ollmann ◽  
...  
Keyword(s):  
Coat Color ◽  
Wild Type Mouse ◽  
Tyrosinase Activity ◽  
Loss Of Function ◽  
Wild Type ◽  
Melanocortin 1 Receptor ◽  
Signaling Protein ◽  
Melanocyte Stimulating Hormone ◽  
Related Proteins ◽  
Stimulating Hormone

The agouti gene codes for agouti signaling protein (ASP), which is temporally expressed in wild-type mouse follicular melanocytes where it induces pheomelanin synthesis. Studies using purified full-length agouti signaling protein has shown that it competes with (α)-melanocyte stimulating hormone for binding to the melanocortin 1 receptor. We have investigated whether ASP binds exclusively to the melanocortin 1 receptor expressed on mouse melanocytes in primary culture, or additionally activates a receptor that has not been identified yet. We have compared the responses of congenic mouse melanocytes derived from C57 BL/6J-E(+)/E(+), e/e, or E(so)/E(so) mice to (alpha)-MSH and/or ASP. E(+)/E(+) melanocytes express the wild-type melanocortin 1 receptor, e/e melanocytes express a loss-of-function mutation in the melanocortin 1 receptor that results in a yellow coat color, and E(so)/E(so) is a mutation that causes constitutive activation of the melanocortin 1 receptor and renders melanocytes unresponsive to (alpha)-melanocyte stimulating hormone. Mouse E(+)/E(+) melanocytes, but not e/e or E(so)/E(so) melanocytes, respond to agouti signaling protein with decreased basal tyrosinase activity, and reduction in levels of tyrosinase and tyrosinase-related proteins 1 and 2. Only in E(+)/E(+) melanocytes does agouti signaling protein abrogate the stimulatory effects of (alpha)-melanocyte stimulating hormone on cAMP formation and tyrosinase activity. These results indicate that a functional melanocortin 1 receptor is obligatory for the response of mammalian melanocytes to agouti signaling protein.

Mesodermal defects and cranial neural crest apoptosis in alpha5 integrin-null embryos

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4309-4319 ◽  
Author(s):  
K.L. Goh ◽  
J.T. Yang ◽  
R.O. Hynes
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Cell Surface Receptor ◽  
Cranial Neural Crest ◽  
Wild Type ◽  
Surface Receptor ◽  
Cranial Neural Crest Cells

Alpha5beta1 integrin is a cell surface receptor that mediates cell-extracellular matrix adhesions by interacting with fibronectin. Alpha5 subunit-deficient mice die early in gestation and display mesodermal defects; most notably, embryos have a truncated posterior and fail to produce posterior somites. In this study, we report on the in vivo effects of the alpha5-null mutation on cell proliferation and survival, and on mesodermal development. We found no significant differences in the numbers of apoptotic cells or in cell proliferation in the mesoderm of alpha5-null embryos compared to wild-type controls. These results suggest that changes in overall cell death or cell proliferation rates are unlikely to be responsible for the mesodermal deficits seen in the alpha5-null embryos. No increases in cell death were seen in alpha5-null embryonic yolk sac, amnion and allantois compared with wild-type, indicating that the mutant phenotype is not due to changes in apoptosis rates in these extraembryonic tissues. Increased numbers of dying cells were, however, seen in migrating cranial neural crest cells of the hyoid arch and in endodermal cells surrounding the omphalomesenteric artery in alpha5-null embryos, indicating that these subpopulations of cells are dependent on alpha5 integrin function for their survival. Mesodermal markers mox-1, Notch-1, Brachyury (T) and Sonic hedgehog (Shh) were expressed in the mutant embryos in a regionally appropriate fashion. Both T and Shh, however, showed discontinuous expression in the notochords of alpha5-null embryos due to (1) degeneration of the notochordal tissue structure, and (2) non-maintenance of gene expression. Consistent with the disorganization of notochordal signals in the alpha5-null embryos, reduced Pax-1 expression and misexpression of Pax-3 were observed. Anteriorly expressed HoxB genes were expressed normally in the alpha5-null embryos. However, expression of the posteriormost HoxB gene, Hoxb-9, was reduced in alpha5-null embryos. These results suggest that alpha5beta1-fibronectin interactions are not essential for the initial commitment of mesodermal cells, but are crucial for maintenance of mesodermal derivatives during postgastrulation stages and also for the survival of some neural crest cells.

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