In the absence of frazzled over-expression of Abelson tyrosine kinase disrupts commissure formation and causes axons to leave the embryonic CNS.

Background: In the Drosophila embryonic nerve cord, the formation of commissures require both the chemoattractive Netrin receptor Frazzled (Fra) and the Abelson (Abl) cytoplasmic tyrosine kinase. Abl binds to the cytoplasmic domain of Fra and loss-of-function mutations in abl enhance fra-dependent commissural defects. To further test Abl's role in attractive signaling, we over-expressed Abl in Fra mutants anticipating rescue of commissures.

Frazzled cytoplasmic P-motifs are differentially required for axon pathway formation in the Drosophila embryonic CNS.

Frazzled is a Netrin-dependent chemoattractive receptor required for axon pathway formation in the developing Drosophila embryonic CNS. The cytoplasmic domain is important and contains three conserved P-motifs (P1, P2, and P3) thought to initiate intracellular signaling cascades and to crosstalk with other receptors during axon pathway formation. Here, we rescue homozygous frazzled embryos by pan-neurally expressing a series of mutants lacking either the cytoplasmic domain or one of the conserved P-motifs and assess the ability of these mutants to rescue frazzled defects in commissural, longitudinal and motor axon pathways.

Frazzled regulation of myosin II activity in the Drosophila embryonic CNS.

Frazzled (Fra) is a chemoattractive guidance receptor regulating the cytoskeletal dynamics underlying growth cone steering at the Drosophila embryonic midline. Here, by genetically evaluating the role of Rho GTPases in Fra signaling in vivo, we uncover a Rho-dependent pathway apparently regulating conventional myosin II activity. Midline crossing errors induced by expressing activated Cdc42(v12) or Rac(v12) are suppressed by a heterozygous loss of fra(4) signaling but, in a Fra(wt) gain-of-function condition, no interaction is detected.