Abstract
The growth factor family of neurotrophins has major roles both inside and outside the nervous system. Here, we report a detailed histological analysis of key phenotypes generated by the ablation of the Kinase D interacting substrate of 220 kDa/Ankyrin repeat-rich membrane spanning (Kidins220/ARMS) protein, a membrane-anchored scaffold for the neurotrophin receptors Trk and p75NTR. Kidins220 is important for heart development, as shown by the severe defects in the outflow tract and ventricle wall formation displayed by the Kidins220 mutant mice. Kidins220 is also important for peripheral nervous system development, as the loss of Kidins220 in vivo caused extensive apoptosis of DRGs and other sensory ganglia. Moreover, the neuronal-specific deletion of this protein leads to early postnatal death, showing that Kidins220 also has a critical function in the postnatal brain.
Highlights
The physiological functions of NTs, extend well beyond the nervous system
As defects in heart development were found in mice lacking NT3,8 TrkC,[9] BDNF6 and TrkB,[7] our results suggest that Kidins[220] has an important role in neurotrophin signaling during embryonic heart development
We have conducted a detailed analysis of heart, central nervous system (CNS) and peripheral nervous system (PNS) development in a novel Kidins220À/À mouse line.[1]
Summary
The physiological functions of NTs, extend well beyond the nervous system. Among the extra-neuronal functions of NTs, which include the development and maintenance of several organs, of particular interest is their role during cardiovascular development. We unveiled an unexpected role of Kidins[220] in brain vascular development, and in heart formation.[1] Here, we sought to characterise in more detail some of the phenotypes displayed by Kidins[220] mutant animals, focusing on cardiovascular and sensory neuron development. These results, together with evidence in the literature, put Kidins[220] at the centre of a complex signaling network, mediating the activation of specific pathways in a cell- and tissue-specific manner
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