Signalling through the Type 1 Insulin-Like Growth Factor Receptor (IGF1R) Interacts with Canonical Wnt Signalling to Promote Neural Proliferation in Developing Brain

• DOI: 10.1042/an20120009
• Publication Date: 2012-05-28T08:34:29Z
• Authors: Qichen Hu; Seong Yong Lee; John R O’Kusky; Ping Ye
• Keywords: Signalling

Signalling through the IGF1R [type 1 IGF (insulin-like growth factor) receptor] and canonical Wnt signalling are two pathways that play critical roles in regulating neural cell generation growth. To determine whether can interact with pathway cells vivo, we studied mutant mice altered signalling. We found blunted expression specifically nestin-expressing (IGF1RNestin-KO mice) abundance of β-catenin was significantly reduced. Blunting also markedly decreased: (i) activity a LacZ (β-galactosidase) reporter transgene responds to nuclear (LacZTCF transgene) (ii) number proliferating precursors. In contrast, overexpressing IGF-I factor I) brain increased LacZTCF transgene. Consistently, treatment embryonic neuron cultures derived from Tg (transgenic) mice. Importantly, increasing IGF1RNestin-KO brains by suppressing GSK3β (glycogen synthase kinase-3β) alleviated phenotypic changes induced deficiency. These includes: retarded growth, reduced precursor proliferation (iii) decreased neuronal number. Our current data, consistent our previous study cultured oligodendrocytes, strongly support concept interacts developing promote proliferation. The interaction plays an important role normal development promoting