Abstract
The Wingless (Wnt)-mediated signals are involved in many important aspects of development of the mammalian cerebral cortex. How Wnts interact with their modulators in cortical development is still unclear. Here, we show that Wnt7a and secreted frizzled-related protein 1 (Sfrp1), a soluble modulator of Wnts, are co-expressed in mouse embryonic cortical neural progenitors (NPs). Knockout of Wnt7a in mice causes microcephaly due to reduced NP population and neurogenesis, and Sfrp1 has an opposing effect compared to Wnt7a. Similar to Dkk1, Sfrp1 decreases the Wnt1 and Wnt7a activity in vitro. Our results suggest that Wnt7a and Sfrp1 play opposite roles to ensure proper NP progeny in the developing cortex.
Highlights
During development of the mammalian central nervous system (CNS), billions of neurons are produced from proliferating neural progenitor (NP) (Rakic, 2009)
The canonical Wnt/β-catenin pathway is required for NP self-renewal and differentiation
Our study shows that Wnt7a and secreted frizzled-related protein 1 (Sfrp1) are co-expressed in cortical NPs and their opposite role is essential for controlling NP expansion and neuronal production
Summary
During development of the mammalian CNS, billions of neurons are produced from proliferating NPs (Rakic, 2009). A number of signaling pathways that regulate the switch and balance between proliferation and differentiation of NPs have been defined, including the Notch, Sonic hedgehog, fibroblast growth factor, TGF-β/Smads, and Wnt pathways (Chenn and Walsh, 1999; Rowitch et al, 1999; Hirabayashi et al, 2004; Joksimovic et al, 2009; Aguirre et al, 2010; Menendez et al, 2011; Rash et al, 2011). The canonical Wnt/β-catenin pathway is required for NP self-renewal and differentiation
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