Enhancer detection and developmental expression of zebrafish <i>sprouty1</i>, a member of the <i>fgf8</i> synexpression group

Komisarczuk, Anna Z.; Topp, Stefanie; Stigloher, Christian; Kapsimali, Marika; Bally‐Cuif, Laure; Becker, Thomas

doi:10.1002/dvdy.21689

Cited by 12 publications

(9 citation statements)

References 53 publications

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“…The vertebrate jaw derives from neural crest cells and activated MAPK signalling is required for proper specification of craniofacial components (Walshe and Mason, 2003; Crump et al, 2004; Wilson et al, 2004; Komisarczuk et al, 2008). Pharyngeal arch development was highly sensitive to PD0325901 treatment, with the most severe phenotype being associated with early and high (0.8–1.0 μM PD0325901) treatment conditions.…”

Section: Resultsmentioning

confidence: 99%

Continual and partial MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish

Anastasaki

Rauen

Patton

2012

Disease Models &Amp; Mechanisms

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SUMMARYCardio-facio-cutaneous (CFC) syndrome is caused by germline mutations in KRAS, BRAF and MEK1/2. The highly selective and potent MEK inhibitors that have been developed as anti-cancer agents hold potential as therapeutics for CFC syndrome. We have previously shown that the effects of CFC mutations on zebrafish gastrulation can be prevented by a 1-hour treatment with MEK inhibitors within a specific developmental time-window. However, MEK activity is essential for normal development and PD0325901 treatment outside this treatment window leads to additional developmental defects in MEK-dependent tissues. We now test ten different doses of PD0325901 at six developmental time points and assess the effects on body axis length, heart development and craniofacial structures in zebrafish embryos. Notably, we find that a continuous low-level dose of PD0325901 that has only minor inhibition of MEK activity can prevent the action of both the common CFC BRAFQ257R kinase-active allele and the BRAFG596V kinase-impaired mutant allele through the first 5 days of development. These results provide a detailed study of the effects of PD0325901 in development and show that, unlike in cancer, which requires robust inhibition of MAPK signalling, a partial reduction in phospho-ERK1/2 activity is sufficient to moderate the developmental effects of BRAFCFC mutations.

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Section: Resultsmentioning

confidence: 99%

Continual and partial MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish

Anastasaki

Rauen

Patton

2012

Disease Models &Amp; Mechanisms

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“…Development 137 (23) signalling during embryogenesis (Furthauer et al, 2001;Komisarczuk et al, 2008;Sivak et al, 2005;Taniguchi et al, 2007), and their pattern of expression is similar to that of fgf8 (see Fig. S2A in the supplementary material).…”

Section: Research Articlementioning

confidence: 89%

Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo

et al. 2010

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SUMMARYDuring development, many organs, including the kidney, lung and mammary gland, need to branch in a regulated manner to be functional. Multicellular branching involves changes in cell shape, proliferation and migration. Axonal branching, however, is a unicellular process that is mediated by changes in cell shape alone and as such appears very different to multicellular branching. Sprouty (Spry) family members are well-characterised negative regulators of Receptor tyrosine kinase (RTK) signalling. Knockout of Spry1, 2 and 4 in mouse result in branching defects in different organs, indicating an important role of RTK signalling in controlling branching pattern. We report here that Spry3, a previously uncharacterised member of the Spry family plays a role in axonal branching. We found that spry3 is expressed specifically in the trigeminal nerve and in spinal motor and sensory neurons in a Brain-derived neurotrophin factor (BDNF)-dependent manner. Knockdown of Spry3 expression causes an excess of axonal branching in spinal cord motoneurons in vivo. Furthermore, Spry3 inhibits the ability of BDNF to induce filopodia in Xenopus spinal cord neurons. Biochemically, we show that Spry3 represses calcium release downstream of BDNF signalling. Altogether, we have found that Spry3 plays an important role in the regulation of axonal branching of motoneurons in vivo, raising the possibility of unexpected conservation in the involvement of intracellular regulators of RTK signalling in multicellular and unicellular branching.

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“…In the zebrafish embryo, expression of spry1, spry2 and spry4 has been reported in the midbrain-hindbrain region at midsomitogenesis stages (Furthauer et al, 2001;Furthauer et al, 2002;Furthauer et al, 2004;Komisarczuk et al, 2008). To further analyse their expression, we performed an in situ hybridisation analysis starting from 80% epiboly.…”

Section: Expression Of the Sprouty Gene Family In The Developing Hindmentioning

confidence: 99%

Hindbrain patterning requires fine-tuning of early krox20 transcription by Sprouty 4

et al. 2011

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SUMMARYVertebrate hindbrain segmentation is an evolutionarily conserved process that involves a complex interplay of transcription factors and signalling pathways. Fibroblast growth factor (FGF) signalling plays a major role, notably by controlling the expression of the transcription factor Krox20 (Egr2), which is required for the formation and specification of two segmental units: rhombomeres (r) 3 and 5. Here, we explore the molecular mechanisms downstream of FGF signalling and the function of Sprouty 4 (Spry4), a negative-feedback regulator of this pathway, in zebrafish. We show that precise modulation of FGF signalling by Spry4 is required to determine the appropriate onset of krox20 transcription in r3 and r5 and, ultimately, rhombomere size in the r3-r5 region. FGF signalling acts by modulating the activity of krox20 initiator enhancer elements B and C; in r5, we show that this regulation is mediated by direct binding of the transcription factor MafB to element B. By contrast, FGF signalling does not control the krox20 autoregulatory element A, which is responsible for amplification and maintenance of krox20 expression. Therefore, early krox20 transcription sets the blueprint for r3-r5 patterning. This work illustrates the necessity for fine-tuning in a common and fundamental patterning process, based on a bistable cell-fate choice involving the coupling of an extracellular gradient with a positive-feedback loop. In this mode of patterning, precision and robustness can be achieved by the introduction of a negative-feedback loop, which, in the hindbrain, is mediated by Spry4.

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Enhancer detection and developmental expression of zebrafish sprouty1, a member of the fgf8 synexpression group

Cited by 12 publications

References 53 publications

Continual and partial MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish

Continual and partial MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish

Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo

Hindbrain patterning requires fine-tuning of early krox20 transcription by Sprouty 4

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