The homeobox transcription factor even-skipped regulates netrin-receptor expression to control dorsal motor-axon projections in Drosophila.
Homeobox transcription-factor codes control motor-neuron subtype identity and dorsal versus ventral axon guidance in both vertebrate and invertebrate nervous systems; however, the specific axon guidance-receptors that are regulated by these transcription factors to control pathfinding are poorly defined. In Drosophila, the Even-skipped (Eve) transcription factor specifies dorsal motor-axon projection through the regulation of unidentified guidance molecules. The Netrins and their attractive and repulsive receptors DCC and Unc-5, respectively, define important conserved cue and receptor families that control growth-cone guidance. In Drosophila, the Netrins and frazzled (the fly homolog of DCC) contribute to motor-axon guidance. Here, using genetics and single-cell mRNA-expression analysis, we show that expression and requirement of different Netrin receptor combinations correlate with distinct dorsal and ventral motor-axon projections in Drosophila. Mis-expression of eve dorsalizes ventral axons in part through the upregulation of Unc-5, whereas loss of eve function in two dorsally projecting motor neurons results in aberrant axon projections and a failure to express Unc-5. Our results support a functional link between the expression of distinct Netrin receptor combinations and the transcriptional control of dorsal motor-axon guidance.
Labrador
Juan Pablo
JP
Department of Neuroscience, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
O'keefe
David
D
Yoshikawa
Shingo
S
McKinnon
Randall D
RD
Thomas
John B
JB
Bashaw
Greg J
GJ
D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D020439:Growth Cones / Q000378:metabolism* / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C052837:eve protein, Drosophila; C000617310:fra protein, Drosophila; D049452:Green Fluorescent Proteins