Induction of inner ear fate by FGF3

Development ◽  
2000 ◽  
Vol 127 (10) ◽  
pp. 2011-2019 ◽  
Author(s):  
V. Vendrell ◽  
E. Carnicero ◽  
F. Giraldez ◽  
M.T. Alonso ◽  
T. Schimmang
Keyword(s):  
Growth Factor ◽  
Inner Ear ◽  
Single Gene ◽  
Ectopic Expression ◽  
Gene Expression Pattern ◽  
Marker Genes ◽  
Loss Of Function ◽  
Surface Ectoderm ◽  
Inner Ear Development

Loss-of-function experiments in avians and mammals have provided conflicting results on the capacity of fibroblast growth factor 3 (FGF3) to act as a secreted growth factor responsible for induction and morphogenesis of the vertebrate inner ear. Using a novel technique for gene transfer into chicken embryos, we have readdressed the role of FGF3 during inner ear development in avians. We find that ectopic expression of FGF3 results in the formation of ectopic placodes which express otic marker genes. The ectopically induced placodes form vesicles which show the characteristic gene expression pattern of a developing inner ear. Ectopic expression of FGF3 also influences the formation of the normal orthotopic inner ear, whereas another member of the FGF family, FGF2, shows no effects on inner ear induction. These results demonstrate that a single gene can induce inner ear fate and reveal an unexpectedly widespread competence of the surface ectoderm to form sensory placodes in higher vertebrates.

scholarly journals Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

2021 ◽  
Vol 22 (12) ◽  
pp. 6497
Author(s):  
Anna Ghilardi ◽  
Alberto Diana ◽  
Renato Bacchetta ◽  
Nadia Santo ◽  
Miriam Ascagni ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hair Cells ◽  
Muscle Fibers ◽  
Underlying Mechanism ◽  
Loss Of Function ◽  
Zebrafish Model ◽  
Developmental Defects ◽  
Inner Ear Development ◽  
Syndromic Hearing Loss

The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear development. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

scholarly journals Role of microRNAs in inner ear development and hearing loss

Gene ◽  
2019 ◽  
Vol 686 ◽  
pp. 49-55 ◽  
Author(s):  
Rahul Mittal ◽  
George Liu ◽  
Sai P. Polineni ◽  
Nicole Bencie ◽  
Denise Yan ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Ear Development ◽  
Inner Ear Development

Role of the EGF receptor pathway in growth and patterning of the Drosophila wing through the regulation of vestigial

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 975-985 ◽  
Author(s):  
R. Nagaraj ◽  
A.T. Pickup ◽  
R. Howes ◽  
K. Moses ◽  
M. Freeman ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Regulatory Gene ◽  
Ectopic Expression ◽  
Wing Disc ◽  
Loss Of Function ◽  
Drosophila Wing ◽  
Expression Studies ◽  
Coordinated Expression ◽  
Wing Pouch

Growth and patterning of the Drosophila wing disc depends on the coordinated expression of the key regulatory gene vestigial both in the Dorsal-Ventral (D/V) boundary cells and in the wing pouch. We propose that a short-range signal originating from the core of the D/V boundary cells is responsible for activating EGFR in a zone of organizing cells on the edges of the D/V boundary. Using loss-of-function mutations and ectopic expression studies, we show that EGFR signaling is essential for vestigial transcription in these cells and for making them competent to undergo subsequent vestigial-mediated proliferation within the wing pouch.

scholarly journals The role of Pax2 in mouse inner ear development

2004 ◽  
Vol 272 (1) ◽  
pp. 161-175 ◽  
Author(s):  
Quianna Burton ◽  
Laura K Cole ◽  
Michael Mulheisen ◽  
Weise Chang ◽  
Doris K Wu
Keyword(s):  
Inner Ear ◽  
Ear Development ◽  
Inner Ear Development

scholarly journals Expression of mouse fibroblast growth factor and fibroblast growth factor receptor genes during early inner ear development

2003 ◽  
Vol 228 (2) ◽  
pp. 267-272 ◽  
Author(s):  
Tracy J. Wright ◽  
Ekaterina P. Hatch ◽  
Hakan Karabagli ◽  
Pinar Karabagli ◽  
Gary C. Schoenwolf ◽  
...  
Keyword(s):  
Growth Factor ◽  
Inner Ear ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Mouse Fibroblast ◽  
Fibroblast Growth ◽  
Ear Development ◽  
Inner Ear Development

scholarly journals Effect of Actin Alpha Cardiac Muscle 1 on the Proliferation and Differentiation of Bovine Myoblasts and Preadipocytes

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3468
Author(s):  
Anqi Li ◽  
Xiaotong Su ◽  
Yuan Tian ◽  
Guibing Song ◽  
Linsen Zan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cardiac Muscle ◽  
Differentially Expressed Gene ◽  
Ectopic Expression ◽  
Control Group ◽  
Marker Genes ◽  
Protein Levels ◽  
Proliferation And Differentiation ◽  
Normal Cell Cycle

Actin Alpha Cardiac Muscle 1 (ACTC1) gene is a differentially expressed gene screened through the co-culture system of myoblasts-preadipocytes. In order to study the role of this gene in the process of proliferation and differentiation of bovine myoblasts and preadipocytes, the methods of the knockdown, overexpression, and ectopic expression of ACTC1 were used in this study. After ACTC1 knockdown in bovine myoblasts and inducing differentiation, the sizes and numbers of myotube formation were significantly reduced compared to the control group, and myogenic marker genes—MYOD1, MYOG, MYH3, MRF4, MYF5, CKM and MEF2A—were significantly decreased (p < 0.05, p < 0.01) at both the mRNA and protein levels of myoblasts at different differentiation stages (D0, D2, D4, D6 and D8). Conversely, ACTC1 overexpression induced the inverse result. After ectopic expression of ACTC1 in bovine preadipocytes and induced differentiation, the number and size of lipid droplets were significantly higher than those of the control group, and the expression of adipogenic marker genes—FABP4, SCD1, PPARγ and FASN—were significantly increased (p < 0.05, p < 0.01) at the mRNA and protein levels of preadipocytes at different differentiation stages. Flow cytometry results showed that both the knockdown and overexpression of ACTC1 inhibited the normal cell cycle of myoblasts; however, ectopic expression of ACTC1 in adipocytes induced no significant cell cycle changes. This study is the first to explore the role of ACTC1 in bovine myogenesis and lipogenesis and demonstrates that ACTC1 promotes the differentiation of bovine myoblasts and preadipocytes, affecting the proliferation of myoblasts.

scholarly journals Human model of IRX5 mutations reveals key role for this transcription factor in ventricular conduction

2020 ◽  
Author(s):  
Zeina R Al Sayed ◽  
Robin Canac ◽  
Bastien Cimarosti ◽  
Carine Bonnard ◽  
Jean-Baptiste Gourraud ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Electrical Conduction ◽  
Sodium Current ◽  
Single Gene ◽  
Gene Mutations ◽  
Cardiac Conduction ◽  
Human Model ◽  
Loss Of Function ◽  
Cardiac Electrical Activity

Abstract Aims Several inherited arrhythmic diseases have been linked to single gene mutations in cardiac ion channels and interacting proteins. However, the mechanisms underlying most arrhythmias, are thought to involve altered regulation of the expression of multiple effectors. In this study, we aimed to examine the role of a transcription factor (TF) belonging to the Iroquois homeobox family, IRX5, in cardiac electrical function. Methods and results Using human cardiac tissues, transcriptomic correlative analyses between IRX5 and genes involved in cardiac electrical activity showed that in human ventricular compartment, IRX5 expression strongly correlated to the expression of major actors of cardiac conduction, including the sodium channel, Nav1.5, and Connexin 40 (Cx40). We then generated human-induced pluripotent stem cells (hiPSCs) derived from two Hamamy syndrome-affected patients carrying distinct homozygous loss-of-function mutations in IRX5 gene. Cardiomyocytes derived from these hiPSCs showed impaired cardiac gene expression programme, including misregulation in the control of Nav1.5 and Cx40 expression. In accordance with the prolonged QRS interval observed in Hamamy syndrome patients, a slower ventricular action potential depolarization due to sodium current reduction was observed on electrophysiological analyses performed on patient-derived cardiomyocytes, confirming the functional role of IRX5 in electrical conduction. Finally, a cardiac TF complex was newly identified, composed by IRX5 and GATA4, in which IRX5 potentiated GATA4-induction of SCN5A expression. Conclusion Altogether, this work unveils a key role for IRX5 in the regulation of human ventricular depolarization and cardiac electrical conduction, providing therefore new insights into our understanding of cardiac diseases.

scholarly journals Filling the Silent Void: Genetic Therapies for Hearing Impairment

2012 ◽  
Vol 2012 ◽  
pp. 1-9
Author(s):  
Joel Sng ◽  
Thomas Lufkin
Keyword(s):  
Inner Ear ◽  
Hearing Impairment ◽  
Hair Cells ◽  
Genetic Disorders ◽  
Environmental Damage ◽  
Inner Ear Development ◽  
Sensory Hair Cells ◽  
And Function ◽  
Function Potential

The inner ear cytoarchitecture forms one of the most intricate and delicate organs in the human body and is vulnerable to the effects of genetic disorders, aging, and environmental damage. Owing to the inability of the mammalian cochlea to regenerate sensory hair cells, the loss of hair cells is a leading cause of deafness in humans. Millions of individuals worldwide are affected by the emotionally and financially devastating effects of hearing impairment (HI). This paper provides a brief introduction into the key role of genes regulating inner ear development and function. Potential future therapies that leverage on an improved understanding of these molecular pathways are also described in detail.

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