Reference Report

Reference
Citation	Serpe, M., O'Connor, M.B. (2006). The metalloprotease tolloid-related and its TGF-beta-like substrate Dawdle regulate Drosophila motoneuron axon guidance. Development 133(24): 4969--4979. (Export to RIS)
FlyBase ID	FBrf0194328
Publication Type	Research paper
PubMed ID	17119021
PubMed Abstract	Proper axon pathfinding requires that growth cones execute appropriate turns and branching at particular choice points en route to their synaptic targets. Here we demonstrate that the Drosophila metalloprotease tolloid-related (tlr) is required for proper fasciculation/defasciculation of motor axons in the CNS and for normal guidance of many motor axons enroute to their muscle targets. Tlr belongs to a family of developmentally important proteases that process various extracellular matrix components, as well as several TGF-beta inhibitory proteins and pro-peptides. We show that Tlr is a circulating enzyme that processes the pro-domains of three Drosophila TGF-beta-type ligands, and, in the case of the Activin-like protein Dawdle (Daw), this processing enhances the signaling activity of the ligand in vitro and in vivo. Null mutants of daw, as well as mutations in its receptor babo and its downstream mediator Smad2, all exhibit axon guidance defects that are similar to but less severe than tlr. We suggest that by activating Daw and perhaps other TGF-beta ligands, Tlr provides a permissive signal for axon guidance.
DOI	10.1242/dev.02711
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Secondary IDs
Language of Publication	English
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Parent Publication
Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Aberrations (1)
	Df(3R)tld-γ1
Alleles (36)
	Actβ^{Act5C.T:SV5\V5,T:Zzzz\His6} babo⁵² daw^{Act5C.T:SV5\V5,T:Zzzz\His6} daw^ex11 daw^ex32 daw^NP4661 daw^Scer\UAS.cSa daw^{tm.Act5C.T:SV5\V5,T:Zzzz\His6} gcm^N7-4 Mad^{Act5C.T:Zzzz\FLAG} myo^{Act5C.T:SV5\V5,T:Zzzz\His6} put⁶² put¹³⁵ Scer\GAL4^12M Scer\GAL4^C321c Scer\GAL4^Cg.PA Scer\GAL4^da.G32 Scer\GAL4^elav-C155 Scer\GAL4^G14 Scer\GAL4^Hml.PG Scer\GAL4^how-24B Scer\GAL4^hs.PB Scer\GAL4^Mhc.PW Scer\GAL4^phm.PO Scer\GAL4^Rapgap1-OK6 Scer\GAL4^sca-109-68 Scer\GAL4^twi.2PE Smox^{Act5C.T:Zzzz\FLAG} Smox^unspecified tld^Scer\UAS.cHa tok^{cd.Scer\UAS.T:Ivir\HA1} tok^E1 tok^{pm.Scer\UAS.T:Ivir\HA1} tok^{Scer\UAS.cSa.T:Ivir\HA1} tok^Δ2-41 w^+mC
Constructs (13)
	P{?GawB} P{Cg-GAL4.A} P{GAL4-da.G32} P{GAL4-Hsp70.PB} P{GAL4-Mhc.W} P{GAL4-twi.2xPE} P{Hml-GAL4.G} P{phm-GAL4.O} P{UAS-daw.S} P{UAS-tld.H} P{UAS-tlr.cd} P{UAS-tlr.pm} P{UAS-tok.S}
Genes (21)
	Actβ Avic\GFP babo Csp daw Fas2 gcm Mad mav myo phm put Scer\GAL4 Smox T:SV5\V5 T:Zzzz\FLAG T:Zzzz\His6 tld tok w wit
Insertions (11)
	P{?GawB}daw^ex32 P{GAL4}G14 P{GawB}12M P{GawB}C321c P{GawB}daw^NP4661 P{GawB}elav^C155 P{GawB}how^24B P{GawB}OK6 P{GawB}sca^109-68 P{UAS-tld.H}16 P{UAS-tld.H}23
Natural transposons (1)
	P-element