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Front Cell Dev Biol 2022 Jan 01;10:981762. doi: 10.3389/fcell.2022.981762.
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FGF-mediated establishment of left-right asymmetry requires Rab7 function in the dorsal mesoderm in Xenopus.

Kreis J , Camuto CM , Elsner CC , Vogel S , Vick P .

Gastrulation denotes a very important developmental process, which includes significant structural tissue rearrangements and patterning events that shape the emerging vertebrate organism. At the end of gastrulation, the three body axes are spatially defined while the left-right axis still lacks any molecular or morphological polarity. In most vertebrates, this is established during neurulation by a symmetry breaking LR organizer. However, this mesoderm-derived structure depends on proper induction and specification of the mesoderm, which in turn requires involvement of several signaling pathways. Endocytosis and the endosomal machinery offer manifold platforms for intracellular pathway regulation, especially late endosomes claim increasing attention. The late endosomal regulator Rab7 has been linked to mesoderm specification during gastrulation. Distinct axial defects due to compromised dorsal mesoderm development in rab7-deficient Xenopus embryos suggested a requirement of Rab7 for FGF-dependent mesoderm patterning and LR asymmetry. Here we specifically addressed such a role of Rab7, demonstrating a functional requirement for LR organizer development and symmetry breakage. Using different FGF/MAPK pathway components we show that Rab7 participates in dorsal mesoderm patterning. We suggest a hierarchical classification of Rab7 upstream of MAPK-dependent mesoderm specification, most probably at the level of the small GTPase Ras. Thus, this study affords an insight on how the Rab7-regulated endosomal machinery could participate in signal transduction to enable correct mesoderm specification and left-right asymmetry.

PubMed ID: 36105355
PMC ID: PMC9465294
Article link: Front Cell Dev Biol

Species referenced: Xenopus laevis
Genes referenced: dand5 ets2 fgf8 fgfr1 foxj1 foxj1.2 h2bc21 mapk1 myf5 myf6 myod1 nodal1 pitx1 pitx2 rab7a tbxt tekt2
GO keywords: MAPK cascade [+]
Antibodies: Mapk1 Ab7
Morpholinos: rab7a MO1

Phenotypes: Xla Wt + ets2 (Fig. S2 E') [+]

Article Images: [+] show captions
References [+] :
Amaya, Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. 1991, Pubmed, Xenbase