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Development 2017 Nov 15;14422:4183-4194. doi: 10.1242/dev.157644.
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PFKFB4 control of AKT signaling is essential for premigratory and migratory neural crest formation.

Figueiredo AL , Maczkowiak F , Borday C , Pla P , Sittewelle M , Pegoraro C , Monsoro-Burq AH .

Neural crest (NC) specification comprises an early phase, initiating immature NC progenitors formation at neural plate stage, and a later phase at neural fold stage, resulting in a functional premigratory NC that is able to delaminate and migrate. We found that the NC gene regulatory network triggers upregulation of pfkfb4 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4) during this late specification phase. As shown in previous studies, PFKFB4 controls AKT signaling in gastrulas and glycolysis rate in adult cells. Here, we focus on PFKFB4 function in NC during and after neurulation, using time-controlled or hypomorph depletions in vivo We find that PFKFB4 is essential both for specification of functional premigratory NC and for its migration. PFKFB4-depleted embryos fail to activate n-cadherin and late NC specifiers, and exhibit severe migration defects resulting in craniofacial defects. AKT signaling mediates PFKFB4 function in NC late specification, whereas both AKT signaling and glycolysis regulate migration. These findings highlight novel and essential roles of PFKFB4 activity in later stages of NC development that are wired into the NC gene regulatory network.

PubMed ID: 29038306
Article link: Development

Species referenced: Xenopus laevis
Genes referenced: acta1 akt1 bmpr1a casp3.2 cdh2 ctnnb1 eef1a1 fgf8 fn1 foxd3 grn h2bc21 hes4 hk1 hoxb9 itk krt12.4 mapk1 msx1 myc myod1 odc1 otx2 pax3 pfkfb1 pfkfb2 pfkfb3 pfkfb4 pfkp pik3ca psmd6 slc12a3 snai2 sox10 sox2 sox9 twist1 wnt7b zic1
GO keywords: neural crest cell migration [+]
Antibodies: Acta1 Ab6 Akt Ab10 Akt1 Ab1 Casp3 Ab1
Morpholinos: ctnnb1 MO1 fgf8 MO1 pax3 MO1 pfkfb4 MO1 pfkfb4 MO2 sox9 MO1 tfap2a MO1

Article Images: [+] show captions