Sprouty2/4 deficiency disrupts early signaling centers
impacting chondrogenesis in the mouse forelimb

J 2025

Sprouty2/4 deficiency disrupts early signaling centers impacting chondrogenesis in the mouse forelimb

DALECKA, Linda; Eva HRUBÁ; Marketa ANDRASOVA; Klara STEKLIKOVA; Zuzana PAVLIKOVA et. al.

Basic information

Original name

Sprouty2/4 deficiency disrupts early signaling centers impacting chondrogenesis in the mouse forelimb

Authors

DALECKA, Linda; Eva HRUBÁ (203 Czech Republic, belonging to the institution); Marketa ANDRASOVA; Klara STEKLIKOVA; Zuzana PAVLIKOVA; Klára KUČEROVÁ (203 Czech Republic, belonging to the institution); Tereza SZOTKOWSKA; Martin BARTOS; Marcela BUCHTOVÁ (203 Czech Republic, belonging to the institution); Abigail Saffron TUCKER and Maria HOVORAKOVA

Edition

JBMR Plus, Wiley, 2025, 2473-4039

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10605 Developmental biology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 3.400 in 2023

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1093/jbmrpl/ziaf002

UT WoS

001412280900001

EID Scopus

2-s2.0-85217717806

Keywords in English

FGF signaling; RTKs; micro-CT; autopodium pathologies; apical ectodermal ridge; zone of polarizing activity; Shh; ciliopathy; limb patterning; genetic animal models

Abstract

V originále

The FGF signaling pathway plays an important role in the regulation of limb development, controlling cell migration, proliferation, differentiation, and apoptosis. Sprouty proteins act as antagonists of the FGF pathway and control the extent of FGF signaling as part of a negative feedback loop. Sprouty2/4 deficient mice evince defects in endochondral bone formation and digit patterning in their forelimbs, with pathogenesis recently related to ciliopathies. To understand the mechanisms behind these pathologies, the limb defects in Sprouty2+/-;Sprouty4-/- male and female mice were characterized and correlated to the dynamic expression patterns of Sprouty2 and Sprouty4, and the impact on the main signaling centers of the limb bud was assessed. Sprouty2 and Sprouty4 exhibited dynamic expressions during limb development. Interestingly, despite similar expression patterns in all limbs, the hindlimbs did not evince any obvious alterations in development, while the forelimbs showed consistent phenotypes of variable severity. Prenatally as well as postnatally, the left forelimb was significantly more severely affected than the right one. A broad variety of pathologies was present in the autopodium of the forelimb, including changes in digit number, size, shape, and number of bones, hand clefts, and digit fusions. Ectopic ossification of bones and abnormal bone fusions detected in micro-CT scans were frequently observed in the digital as well as in the carpal and metacarpal areas. Sprouty2+/-;Sprouty4-/- limb buds showed patchy loss of Fgf8 expression in the apical ectodermal ridge, and a loss of tissue underlying these regions. The zone of polarizing activity was also impacted, with lineage analysis highlighting a change in the contribution of Sonic hedgehog expressing cells. These findings support the link between Sproutys and Hedgehog signaling during limb development and highlight the importance of Sprouty2 and Sprouty4 in controlling early signaling centers in the limb.

Links

GA21-04178S, research and development project

Name: Propojení funkce Sprouty s FGF a primárními ciliemi ve vývoji

Investor: Czech Science Foundation

Cite

DALECKA, Linda; Eva HRUBÁ; Marketa ANDRASOVA; Klara STEKLIKOVA; Zuzana PAVLIKOVA; Klára KUČEROVÁ; Tereza SZOTKOWSKA; Martin BARTOS; Marcela BUCHTOVÁ; Abigail Saffron TUCKER and Maria HOVORAKOVA. Sprouty2/4 deficiency disrupts early signaling centers impacting chondrogenesis in the mouse forelimb. JBMR Plus. Wiley, 2025, vol. 9, No 3, p. 1-16. ISSN 2473-4039. Available from: https://dx.doi.org/10.1093/jbmrpl/ziaf002.

@article{2476297,
   author = {Dalecka, Linda and Hrubá, Eva and Andrasova, Marketa and Steklikova, Klara and Pavlikova, Zuzana and Kučerová, Klára and Szotkowska, Tereza and Bartos, Martin and Buchtová, Marcela and Tucker, Abigail Saffron and Hovorakova, Maria},
   article_number = {3},
   doi = {http://dx.doi.org/10.1093/jbmrpl/ziaf002},
   keywords = {FGF signaling; RTKs; micro-CT; autopodium pathologies; apical ectodermal ridge; zone of polarizing activity; Shh; ciliopathy; limb patterning; genetic animal models},
   language = {eng},
   issn = {2473-4039},
   journal = {JBMR Plus},
   title = {Sprouty2/4 deficiency disrupts early signaling centers impacting chondrogenesis in the mouse forelimb},
   url = {https://academic.oup.com/jbmrplus/article/9/3/ziaf002/7950993},
   volume = {9},
   year = {2025}
}

TY  - JOUR
ID  - 2476297
AU  - Dalecka, Linda - Hrubá, Eva - Andrasova, Marketa - Steklikova, Klara - Pavlikova, Zuzana - Kučerová, Klára - Szotkowska, Tereza - Bartos, Martin - Buchtová, Marcela - Tucker, Abigail Saffron - Hovorakova, Maria
PY  - 2025
TI  - Sprouty2/4 deficiency disrupts early signaling centers impacting chondrogenesis in the mouse forelimb
JF  - JBMR Plus
VL  - 9
IS  - 3
SP  - 1-16
EP  - 1-16
PB  - Wiley
SN  - 24734039
KW  - FGF signaling
KW  - RTKs
KW  - micro-CT
KW  - autopodium pathologies
KW  - apical ectodermal ridge
KW  - zone of polarizing activity
KW  - Shh
KW  - ciliopathy
KW  - limb patterning
KW  - genetic animal models
UR  - https://academic.oup.com/jbmrplus/article/9/3/ziaf002/7950993
N2  - The FGF signaling pathway plays an important role in the regulation of limb development, controlling cell migration, proliferation, differentiation, and apoptosis. Sprouty proteins act as antagonists of the FGF pathway and control the extent of FGF signaling as part of a negative feedback loop. Sprouty2/4 deficient mice evince defects in endochondral bone formation and digit patterning in their forelimbs, with pathogenesis recently related to ciliopathies. To understand the mechanisms behind these pathologies, the limb defects in Sprouty2+/-;Sprouty4-/- male and female mice were characterized and correlated to the dynamic expression patterns of Sprouty2 and Sprouty4, and the impact on the main signaling centers of the limb bud was assessed. Sprouty2 and Sprouty4 exhibited dynamic expressions during limb development. Interestingly, despite similar expression patterns in all limbs, the hindlimbs did not evince any obvious alterations in development, while the forelimbs showed consistent phenotypes of variable severity. Prenatally as well as postnatally, the left forelimb was significantly more severely affected than the right one. A broad variety of pathologies was present in the autopodium of the forelimb, including changes in digit number, size, shape, and number of bones, hand clefts, and digit fusions. Ectopic ossification of bones and abnormal bone fusions detected in micro-CT scans were frequently observed in the digital as well as in the carpal and metacarpal areas. Sprouty2+/-;Sprouty4-/- limb buds showed patchy loss of Fgf8 expression in the apical ectodermal ridge, and a loss of tissue underlying these regions. The zone of polarizing activity was also impacted, with lineage analysis highlighting a change in the contribution of Sonic hedgehog expressing cells. These findings support the link between Sproutys and Hedgehog signaling during limb development and highlight the importance of Sprouty2 and Sprouty4 in controlling early signaling centers in the limb.
ER  -

DALECKA, Linda; Eva HRUBÁ; Marketa ANDRASOVA; Klara STEKLIKOVA; Zuzana PAVLIKOVA; Klára KUČEROVÁ; Tereza SZOTKOWSKA; Martin BARTOS; Marcela BUCHTOVÁ; Abigail Saffron TUCKER and Maria HOVORAKOVA. Sprouty2/4 deficiency disrupts early signaling centers impacting chondrogenesis in the mouse forelimb. \textit{JBMR Plus}. Wiley, 2025, vol.~9, No~3, p.~1-16. ISSN~2473-4039. Available from: https://dx.doi.org/10.1093/jbmrpl/ziaf002.

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