Sonic Hedgehog and Notch Signaling Can Cooperate to Regulate Neurogenic Divisions of Neocortical Progenitors

Innate lymphoid cells (ILCs) and innate-like lymphocytes have important roles in immune responses in the context of infection, cancer, and autoimmunity. The factors involved in driving the differentiation and function of these cell types remain to be clearly defined. There are several cellular signaling pathways involved in embryogenesis, which continue to function in adult tissue. In particular, the WNT, NOTCH, and Hedgehog signaling pathways are emerging as regulators of hematopoietic cell development and differentiation. This review discusses the currently known roles of WNT, NOTCH, and Hedgehog signaling in the differentiation and function of ILCs and innate-like lymphocytes

The Notch3 receptor and its intracellular signaling-dependent oncogenic mechanisms

During evolution, gene duplication of the Notch receptor suggests a progressive functional diversification. The Notch3 receptor displays a number of structural differences with respect to Notch1 and Notch2, most of which have been reported in the transmembrane and in the intracellular regions, mainly localized in the negative regulatory region (NRR) and trans-activation domain (TAD). Targeted deletion of Notch3 does not result in embryonic lethality, which is in line with its highly restricted tissue expression pattern. Importantly, deregulated Notch3 expression and/or activation, often results in disrupted cell differentiation and/or pathological development, most notably in oncogenesis in different cell contexts. Mechanistically this is due to Notch3-related genetic alterations or epigenetic or posttranslational control mechanisms. In this chapter we discuss the possible relationships between the structural differences and the pathological role of Notch3 in the control of mouse and human cancers. In future, targeting the unique features of Notch3-oncogenic mechanisms could be exploited to develop anticancer therapeutics