Dale Frank, PhD
Associate Professor of Biochemistry
PhD, 1989 - Hebrew University, Jerusalem
How do cells acquire different cell-fates in the developing vertebrate embryo?
During early development, cells respond to local non-autonomous signals, which "induce" formation of the prototypical body structure: the head/tail, back/stomach, and left/right axes. Then, cells must "define" their identities in the embryo, whether to become muscle, blood or nerve tissues. In the nervous system, cells in the anterior/head become brain neurons or eye cells, whereas cells in the posterior/tail become motor-neurons. Correct cell-fate is dependent on each cell’s ability to interpret its relative position along the embryonic body-axes. In every cell, transcription factor proteins direct both inductive and non-autonomous cell-fate decisions. Early developmental regulation in all vertebrate species (from humans to fish) is carried out by homologous gene products. In my lab, we utilize the frog, Xenopus laevis, as our model vertebrate system to elucidate how Meis-family homebox transcription factors interact with signaling pathways to regulate cell-fate decisions that pattern early nervous system development. For more information see my Lab webpage: http://dal320.wix.com/dale-frank-froglab-1
Bin-Nun N, Lichtig H, Malyarova A, Levy M, Elias S, and Frank D. 2014. PTK7 modulates Wnt signaling activity via LRP6. Development 141, 410-421.
Schulte D and Frank D. 2014. Review: TALE transcription factors during early development of the vertebrate brain and eye. Dev Dyn. 243, 99-116.
Elkouby YM, Polevoy H, Gutkovich YE, Michaelov A, and Frank D. 2012. A hindbrain-repressive Wnt3a/Meis3/Tsh1 circuit promotes neuronal differentiation and coordinates tissue maturation. Development 139, 1487-1497.
Fonar Y, Gutkovich YE, Root H, Malyarova A, Aamar E, Golubovskaya VM, Elias S, Elkouby YM, and Frank, D. 2011. Focal Adhesion Kinase protein regulates Wnt3a gene expression to control cell fate specification in the developing neural plate. Mol. Biol. Cell 22, 2409-2421.
Elkouby YM, Elias S, Casey EM, Blythe SA, Tsabar N, Klein PS, Root H, Liu KJ, and Frank D. 2010. Mesodermal Wnt signaling organizes the neural plate via Meis3. Development 137, 1531-1541.
Meis3 protein restores posterior neural cell fates in the absence of canonical Wnt signaling.
Left panel: Morphology of mid-late neurula embryos (a) injected at the one-cell stage with either Wnt3a Morpholino (MO) (b), or Meis3 mRNA (c), or doubly-injected with both (d). Neural plate folding and convergence extension-elongation is strongly-inhibited in Wnt3a morphant embryos (b); Meis3 co-expression rescued this phenotype (d). All embryos are viewed dorsally, and oriented with anterior at the top, posterior at the bottom.
Right panel: In situ hybridization of mid-late neurula embryos (a,e,i,m,q) injected at the one-cell stage with either Wnt3a-MO (b,f,j,n,r), or separately with Meis3 mRNA (d,h,l,p,t) or doubly-injected with both (c,g,k,o,s). Anterior-forebrain-specific XAnf1 expression is posteriorly expanded in Wnt3a-morphants (b), and suppressed by Meis3 co-expression (c,d). Expression of the posterior neural markers Krox20 (hindbrain), HoxB3 (hindbrain), N-Tub (primary neuron) and FoxD3 (neural crest) is inhibited in Wnt3a-morphants (f,j,n,r), but rescued by Meis3 co-expression (g,k,o,s). All embryos are viewed dorsally, and oriented with anterior at the top, posterior at the bottom.
Meis3 protein restores posterior neural cell fates in the absence of canonical Wnt signaling