Browsing by Subject "FGF"

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Intracellular regulation of Wnt and FGF signal transduction by the late endosomal compartment in Xenopus laevis
(2022) Kreis, Jennifer; Feistel, Kerstin
The endosomal network depicts a vast playground of multiple processing capabilities in terms of signaling. Distinct compartments of the endosomal machinery exert specific functions and thus contribute in signal termination, transduction, attenuation or amplification. Initially, these functions were attributed to early endosomes but recent research likewise considers late endosomes to be just as relevant in mediating such processes. Functionality as well as the molecular identity of these intracellular membranous platforms are orchestrated by a large superfamily of small Ras like GTPases. The collected data of this study particularly highlight the involvement of late endosomes and its associated regulator Rab7 in the early development of the African clawed frog Xenopus laevis. In particular, the first two chapters address the Rab7-dependent specification of the mesodermal germ layer by regulating intracellular pathway activity of Wnt and FGF/MAPK signaling. After fertilization formation of the germ layers is one of the first processes to be initiated. An essential part of mesoderm development comprises subdivision into different mesodermal regions, thus clustering it into ventrolateral and dorsal mesoderm. This patterning is crucial to promote further differentiation into various tissues arising from the mesodermal germ layer. It turned out, Rab7 regulates ventrolateral fates in a Wnt-dependent manner. The small GTPase exerts its function upstream of the Wnt co-transcription factor Ctnnb1 to ensure its nuclear relocalization. In addition to that, Rab7-positive endosomes are likewise required to mediate intracellular FGF/MAPK signal transduction in order to specify dorsal mesoderm. Here, Rab7 regulates proper signaling at the level or downstream of Ras and upstream of Erk/Mapk1. The last chapter then elicits further regulative properties of the late endosomal platform, concerning Cd63 function. The tetraspanin Cd63, which constitutes a transmembrane protein, associates with late endolysosomal compartments and exhibits a similar expression pattern like the small GTPase Rab7 in Xenopus laevis. Contrary to Rab7, function of Cd63 seems to be dispensable whilst gastrulation. However, the presented studies in this chapter suggest a vital function of the tetraspanin Cd63 during axial elongation and correct eye development. Therefore, these investigations regarding Cd63 demonstrated an involvement of the regulative function of late endosomes as signaling platforms for embryonic development beyond mesoderm specification and gastrulation. Overall, the summarized data of this study provides further insights into the determining capacity of Rab7-positive endosomal platforms in intracellular signal transduction of different pathways during early embryonic development.