Publication detail

Deficiency of Sprouty Proteins in Mice Resemble Ciliopathic Phenotype

HRUBÁ, E. KAVKOVÁ, M. ZIKMUND, T. BUCHTOVÁ, M.

Original Title

Deficiency of Sprouty Proteins in Mice Resemble Ciliopathic Phenotype

Type

presentation, poster

Language

English

Original Abstract

The Sprouty family of proteins is a highly conserved group of intracellular modulators of receptor tyrosine kinase signaling, including the fibroblast growth factor receptor (FGFR) pathway. There are four orthologs (Sprouty1-4) in mammals. During embryonic development and postnatal bone remodeling, tight regulation of FGFR signaling is essential in endochondral ossification and in bone and mineral homeostasis. Sprouty2 was shown to be implicated in endochondral bone formation in Sprouty2-/- mice with reduced postnatal skeletal size and trabecular bone mass. Nevertheless, the underlying mechanism of its action at the molecular level remains to be elucidated. Moreover, long bones of Sprouty4-/- display limb malformations, such as chondroma-like lesions in locations adjacent to growth plate, or fused and/or supernumerary digits on front limbs. Our skeletal and other phenotypic findings on Sprouty2- and 4-deficient mice and Sprouty2/4 double knockouts (DKOs) strikingly resemble the phenotype of model mice bearing mutations in genes associated with primary cilia structure and function. Furthermore, in vivo evidence for disruption of primary cilia length was reported in achondroplasia and thanatophoric dysplasia cartilage growth plates with sustained activation of FGF signaling. Moreover, new links between ciliopathies and FGF-related syndromes have been discovered recently. Indeed, our analysis of Sprouty2-/- and Sprouty2/4 DKO embryonic and postnatal growth plates revealed elongation of ciliary axonemes compared to corresponding wildtype tissues and expression of several genes associated with ciliogenesis were downregulated in embryonic Sprouty2-/- tissue. Taken together, we propose that Sprouty proteins deficient mice may be actually ciliopathic in nature and that they represent a valuable model for studying the association of FGF signaling overactivation and cilia dysfunction, not only in skeletogenesis.

Keywords

Conference poster

Authors

HRUBÁ, E.; KAVKOVÁ, M.; ZIKMUND, T.; BUCHTOVÁ, M.

Released

3. 6. 2019

Publisher

Wiley

ISBN

0362-2525

Periodical

JOURNAL OF MORPHOLOGY

Year of study

280

State

United States of America

Pages from

141

Pages to

141

Pages count

244

URL

https://onlinelibrary.wiley.com/doi/abs/10.1002/jmor.21003

BibTex

@misc{BUT157894,
  author="Eva {Hrubá} and Michaela {Kavková} and Tomáš {Zikmund} and Marcela {Buchtová}",
  title="Deficiency of Sprouty Proteins in Mice Resemble Ciliopathic Phenotype",
  year="2019",
  journal="JOURNAL OF MORPHOLOGY",
  volume="280",
  pages="141--141",
  publisher="Wiley",
  issn="0362-2525",
  url="https://onlinelibrary.wiley.com/doi/abs/10.1002/jmor.21003",
  note="presentation, poster"
}