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XB-ART-42324
Development December 1, 2010; 137 (23): 4005-15.

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

Panagiotaki N , Dajas-Bailador F , Amaya E , Papalopulu N , Dorey K .


Abstract
During 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.

PubMed ID: 21062861
PMC ID: PMC2976284
Article link: Development
Grant support: [+]
Genes referenced: bdnf ddr1 fgf8 mnx1 ntrk2 odc1 rpl8 spry1 spry2 spry3 spry4 tlx3 tuba4b
Antibodies: Tuba4b Ab5
Morpholinos: ntrk2 MO1 spry3 MO1 spry3 MO2


Article Images: [+] show captions
References [+] :
Acebes, Cellular and molecular features of axon collaterals and dendrites. 2000, Pubmed


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