wnt5a regulates midbrain dopaminergic axon growth and guidancewnt5a调节中脑多巴胺能轴突生长和指导.pdfVIP

Wnt5a Regulates Midbrain Dopaminergic Axon Growth and Guidance 1,2 1 1 1,2,3 Brette D. Blakely , Christopher R. Bye , Chathurini V. Fernando , Malcolm K. Horne , 4¤ 4¤ 5 1,2 Maria L. Macheda , Steven A. Stacker , Ernest Arenas , Clare L. Parish * 1 Florey Neuroscience Institutes, The University of Melbourne, Victoria, Australia, 2 Centre for Neurosciences, The University of Melbourne, Victoria, Australia, 3 St Vincent’s Hospital, Fitzroy, Victoria, Australia, 4 Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria, Australia, 5 Laboratory of Molecular Neurobiology, Department of Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden Abstract During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM) the cues that guide dopaminergic (DA) axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary