Netrin 1-mediated chemoattraction regulates the migratory pathway of LHRH neurons

被引:65
作者
Schwarting, GA
Raitcheva, D
Bless, EP
Ackerman, SL
Tobet, S
机构
[1] Eunice Kennedy Shriver Ctr Mental Retardat Inc, UMMS, Waltham, MA 02452 USA
[2] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA
[3] Jackson Lab, Bar Harbor, ME 04609 USA
[4] Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA
[5] Colorado State Univ, Coll Vet Med & Biomed Sci, Ft Collins, CO 80523 USA
关键词
axon guidance; cell migration; gonadotrophin-releasing hormone; luteinizing hormone-releasing hormone; netrin; 1; vomeronasal;
D O I
10.1111/j.1460-9568.2004.03094.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Luteinizing hormone-releasing hormone (LHRH) neurons migrate from the vomeronasal organ (VNO) to the forebrain in all mammals studied. In mice, the direction of LHRH neuron migration is dependent upon axons that originate in the VNO, but bypass the olfactory bulb and project caudally into the basal forebrain. Thus, factors that guide this unique subset of vomeronasal axons that comprise the caudal vomeronasal nerve (cVNN) are candidates for regulating the migration of LHRH neurons. We previously showed that deleted in colorectal cancer (DCC) is expressed by neurons that migrate out of the VNO during development [Schwarting et al. (2001) J. Neurosci., 21, 911-919]. We examined LHRH neuron migration in Dcc(-/-) mice and found that trajectories of the cVNN and positions of LHRH neurons are abnormal. Here we extend these studies to show that cVNN trajectories and LHRH cell migration in netrin 1 (Ntn1) mutant mice are also abnormal. Substantially reduced numbers of LHRH neurons are found in the basal forebrain and many LHRH neurons migrate into the cerebral cortex of Ntn1 knockout mice. In contrast, migration of LHRH cells is normal in Unc5h3(rcm) mutant mice. These results are consistent with the idea that the chemoattraction of DCC+ vomeronasal axons by a gradient of netrin 1 protein in the ventral forebrain guides the cVNN, which, in turn, determines the direction of LHRH neuron migration in the forebrain. Loss of function through a genetic deletion in either Dcc or Ntn1 results in the migration of many LHRH neurons to inappropriate destinations.
引用
收藏
页码:11 / 20
页数:10
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