Roundabout gene family functions during sensory axon guidance in the drosophila embryo are mediated by both Slit-dependent and Slit-independent mechanisms

Abstract

roundabout (robo) family genes play key roles in axon guidance in a wide variety of animals. We have investigated the roles of the robo family members, robo, robo2, and robo3, in the guidance of sensory axons in the Drosophila embryo. In robo(-/-), slit(-/-), and robo(-/+) slit(-/+) mutants, lateral cluster sensory neurons misproject to cells and axons in the nearby ventral' (v') cluster. These phenotypes, together with the normal expression pattern of Slit and Robo, suggest that Slit ligand secreted from the epidermis interacts with Robo receptors on lateral cluster sensory growth cones to limit their exploration of nearby attractive substrates. The most common sensory axon phenotype seen in robo2(-/-) mutants was misprojection of dorsal cluster sensory axons away from their normal growth substrate, the transverse connective of the trachea. slit appears to play no role in this aspect of sensory axon growth. Robo2 is expressed, not on the dorsal sensory axons, but on the transverse connective. These results suggest a novel, non-cell-autonomous mechanism for axon guidance by robo family genes: Robo2 expressed on the trachea acts as an attractant for the dorsal sensory growth cones.

A genetic screen for mutations affecting gonad formation in Drosophila reveals a role for the slit/robo pathway

“…Though their mutant phenotypes are similar, ROBO and ROBO2 have slightly different localizations, with ROBO more prominent between SGPs and GCs, and ROBO2 between SGPs as well as between SGPs and GCs. This suggests potentially distinct functions, and would be consistent with other reports that the Robos perform separate functions (Englund et al, 2002; Parsons et al, 2003; Rajagopalan et al, 2000a; Rajagopalan et al, 2000b; Simpson et al, 2000a; Simpson et al, 2000b). On the other hand, slit mutants have stronger compaction and SGP cluster fusion defects than mutants for any one robo (Fig.…”

“…7B) and suggests that ROBO functions in cell contacts between SGPs and GCs. ROBO2 was expressed in the gonad as well as in several immediately surrounding tissues including the trachea (as previously reported (Parsons et al, 2003)). Its expression levels within the gonad increased as the gonad formed (Fig.…”

Ephrin‐A4 inhibits sensory neurite outgrowth and is regulated by neonatal skin wounding

“…There is evidence for this in the chick, where the embryonic epidermis secretes chondroitin sulphate proteoglycan leading to neurite avoidance (Fichard et al ., 1991) and expresses high levels of brain‐derived neurotrophic factor which has been shown to repel cutaneous axons in the chick (Cahoon‐Metzger et al ., 2001). In embryonic Drosophila slit ligand secreted from epidermis has been shown to interact with Robo receptors on sensory growth cones to limit their exploration of nearby attractive substrates (Parsons et al ., 2003). There is also evidence in the chick that Eph‐A receptors are present on DRG neurons during embryonic development and respond to the presence of ephrin‐A5 in the skin (Munoz et al ., 2005).…”

“…receptors on sensory growth cones to limit their exploration of nearby attractive substrates (Parsons et al, 2003). There is also evidence in the chick that Eph-A receptors are present on DRG neurons during embryonic development and respond to the presence of ephrin-A5 in the skin (Munoz et al, 2005).…”

Drosophilaas a genetic and cellular model for studies on axonal growth

“…While at least two morphological screens have been performed to uncover such genes [25,30], our understanding of the molecular basis for sensory axon guidance is still limited. Nonetheless, several factors that guide motor axons in the periphery and interneuronal axons in the CNS have been shown to play a role in sensory axon guidance, such as Delta and its receptor Notch [197], the actin-microtubule linker molecule Short stop/Kakapo [25,202], Slit and its cognate receptors Robo and Robo2 [203], and the secreted Semaphorin, Sema2a and its receptors Plexin B and Plexin A [204]. …”