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Cell Rep 2021 Jun 22;3512:109289. doi: 10.1016/j.celrep.2021.109289.
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BMP signaling is enhanced intracellularly by FHL3 controlling WNT-dependent spatiotemporal emergence of the neural crest.

Alkobtawi M , Pla P , Monsoro-Burq AH .

The spatiotemporal coordination of multiple morphogens is essential for embryonic patterning yet poorly understood. During neural crest (NC) formation, dynamic bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and WNT signals cooperate by acting on mesoderm and ectoderm. Here, we show that Fhl3, a scaffold LIM domain protein, modulates BMP gradient interpretation during NC induction. During gastrulation, low BMP signaling neuralizes the neural border (NB) ectoderm, while Fhl3 enhances Smad1 intracellular response in underlying paraxial mesoderm, triggering the high WNT8 signals needed to pattern the NB. During neurulation, fhl3 activation in NC ectoderm promotes simultaneous high BMP and BMP-dependent WNT activity required for specification. Mechanistically, Fhl3 interacts with Smad1 and promotes Smad1 binding to wnt8 promoter in a BMP-dependent manner. Consequently, differential Fhl3 expression in adjacent cells ensures a finely tuned coordination of BMP and WNT signaling at several stages of NC development, starting by positioning the NC-inducing mesoderm center under competent NB ectoderm.

PubMed ID: 34161771
Article link: Cell Rep

Species referenced: Xenopus laevis
Genes referenced: babam2 bmp4 dusp5 eef1a2 ephb2 fhl3 foxd3 krt12.4 msx1 myf5 myod1 nog pax3 rps3a smad1 snai2 sox10 sox2 tbxt tcf3 tfap2a twist1 ventx1.2 wnt8a zic1
Antibodies: Acta1 Ab6 Anti-FHL3 Anti-FLAG Anti-FLAG M2 Digoxigenin AB1 Smad1 Ab7
Morpholinos: fhl3 MO1 fhl3 MO2
gRNAs referenced: fhl3 gRNA1

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