split ends, a new component of the Drosophila EGF receptor pathway, regulates development of midline glial cells

Signaling by DER, the Drosophila epidermal growth factor receptor tyrosine kinase (RTK), is essential for proper migration and survival of midline gli al cells (MGCs) in the embryonic central nervous system (CNS) [1-4]. We rec ently isolated a gene called split ends (spen) in a screen designed to iden tify new components of the RTK/Ras pathway [5], Drosophila Spen and its ort hologs are characterized by a distinct set of RNA recognition motifs (RRMs) and a SPOC domain, a highly conserved carboxy-terminal domain of unknown f unction [5-7]. To investigate spen function in the context of RTK signaling , we examined the consequences of spen loss-of-function mutations on embryo nic CNS development. We found that spen was required for normal migration a nd survival of MGCs and that embryos lacking spen had CNS defects strikingl y reminiscent of those seen in mutants of several known components of the D ER signaling pathway. In addition, spen interacted synergistically with the RTK effector pointed. Using MGC-targeted expression, we found that increas ed Ras signaling rescued the lethality associated with expression of a domi nant negative spen transgene, Therefore, spen encodes a positively acting c omponent of the DER/Ras signaling pathway. (C) 2000 Elsevier Science Ltd. A il rights reserved.