Disruption of Esrom and Ryk identifies the roof plate boundary as an intermediate target for commissure formation.
Growth cones are guided to their final destination by intermediate targets. Here, we identify intermediate targets and signaling components acting on zebrafish habenula commissural axons. Live imaging establishes that axons pause at the medial habenula before and after crossing the roof plate. esrom mutants axons fail to advance beyond the ipsilateral medial habenula. Tsc2 function is reduced in mutant axons, indicating cell autonomous defects in signaling. Consistent with signaling properties changing outside the roof plate, EphB is surface localized on axon segments within a zone demarcated by the medial habenula. wnt4a is expressed in the medial habenula and morpholino knockdown causes loss of the commissure. Electroporation of truncated Ryk causes axons to reenter the midline after reaching the contralateral habenula. These data identify Esrom as a mediator of growth cone navigation at an intermediate target and underscore the importance of midline boundaries as signaling centers for commissure formation.
Hendricks
Michael
M
Developmental Neurobiology Group, Temasek Life Sciences Laboratory, 1 Research Link, 117604, Singapore.
Mathuru
Ajay Sriram
AS
Wang
Hui
H
Silander
Olin
O
Kee
Michelle Zhi Ling
MZ
Jesuthasan
Suresh
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D007839:Functional Laterality / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D019262:Habenula / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D018715:Microscopy, Video; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011817:Rabbits; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060528:Wnt4 Protein; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C000624654:Tsc2 protein, mouse; C583920:Tsc2 protein, zebrafish; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D029961:Zebrafish Proteins; C497200:mycbp2 protein, zebrafish; D006899:Mixed Function Oxygenases; D020794:Receptor Protein-Tyrosine Kinases; D036081:Receptors, Eph Family; C118148:Ryk protein, mouse