Mouse notch: expression in hair follicles correlates with cell fate determination.

Abstract

Abstract. Many vertebrate tissues, including skin, are known to develop as a consequence of epithelialmesenchymal interactions. Much less is known about the role of cell-cell interaction within the epithelial or the mesenchymal compartments in morphogenesis. To investigate cell-cell interactions during skin development, and the potential role of the Notch homolog in this process, we cloned the mouse homolog of Notch (mNotch) and studied its expression pattern, starting as early as mesoderm formation. The novel application of double-labeled in situ hybridization in vertebrates allowed high resolution analysis to follow the fate of mNotch expressing cells directly. In comparison with the distribution of Id mRNA, analysis confirmed that in the hair follicle high levels of mNotch are expressed exclusively in the epithelial compartment. Hair follicle matrix cells start expressing mNotch as different cell types become distinguishable in the developing follicle, mNotch mRNA expression persists throughout the growth phase of the follicle and maintains the same expression profile in the second hair cycle. The cells in the follicle that undergo a phase of high level mNotch expression are in transition from mitotic precursors to several discreet, differentiating cell types. Our observations point out that both in time (during development) and in space (by being removed one cell layer from the dermal papilla) mNotch expression is clearly separated from the inductive interactions. This is a novel finding and suggests that mNotch is important for follicular differentiation and possibly cell fate selection within the follicle.

Involvement of Notch1 in the development of mouse mammary tumors

“…The Notch1 probe K was excised from the KS-Motch plasmid (Kopan and Weintraub, 1993). The Notch1 probe J is a 560 bp NcoI ± NcoI fragment of pMN7 (Reaume et al, 1992).…”

“…Z11886; (Del Amo et al, 1993)). Mutant A was constructed by ligating a BamHI ± BclI fragment of pMN7 (nt 5051 ± nt 5553) (Reaume et al, 1992) with a BclI-EcoRI fragment of pKS Motch (nt 5553 ± nt 8064) (Kopan and Weintraub, 1993). Mutant B (DCys) was deleted of the Nterminal part to the SspI site (nt 5187).…”

Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis.

“…In Xenopus, expression of a gain-of-function truncated mutant (harboring only the intracellular domain) of X-Notch affects normal development (Coffman et al 1993) and prevents retinal cell differentiation (Dorsky et al 1995). In mammals, three Notch-related genes have been identified: Notchl, Notch2, and Notch3 (Ellisen et al 1991;Weinmaster et al 1991;Del Am• et al 1992;Reaume et al 1992;Weinmaster et al 1992;Lardelli and Lendahl 1993;Kopan and Weintraub 1993;Lardelli et al 1994), and Notchl also appears to control cell-fate determination (Kopan and Weintraub 1993;Kopan et al 1994;Nye et al 1994). Recent studies have shown that Notch signaling pathways have been preserved from Drosophila to mammals and involve binding to the CBF-1/RBP-JK trans-activator (Hsieh and Hayward 1995;Jarriault et al 1995).…”

Biology of Human Hair: Know Your Hair to Control It

“…The Notch signaling pathway is also important for determining cell fate in HF development [87]. Notch signaling acts by blocking cell differentiation, which maintains the competence of undifferentiated cells [88,89] in both the developing tooth and the HF to respond to inductive signals that determine their developmental fate [87,90].…”

“…Notch signaling acts by blocking cell differentiation, which maintains the competence of undifferentiated cells [88,89] in both the developing tooth and the HF to respond to inductive signals that determine their developmental fate [87,90]. Based on expression studies in the HF, Notch may be a competence factor, as its pattern of expression in the HF appears to be restricted to cells that have left the proliferative pool but have yet to terminally differentiate [91,92].…”