Guide Molecules for GnRH Neuronal Migration

Guide Molecules for GnRH Neuronal Migration

1. ANOS/KAL1

   • An X-linked cell adhesion molecule
   • Mutation Consequences
     • No puberty
     • No GnRH neuronal migration → Forebrain
     • Hypogonadotropic hypogonadism
     • Anosmia
       • AKA Kallmann Syndrome
       • Impacts migration of olfactory neurons

2. FGF8 + FGF1R

   • An autosomal dominant linked guide mlc

3. PROK2 + PROK2R

   • An autosomal recessive linked guide mlc
   • Mutation Consequences
     • KO mice → Tangled webs of olfactory/GnRH neurons
       • Function: Prevents GnRH migration beyond VNO placode

4. Nasal Embryonic LHRH Factor

   • AKA NSMF
   • Expressed in VNO fibers, migrating GnRH neurons
   • Mutation Consequences
     • Antisense KOs ⊣ GnRH Migration beyond VNO

5. Stromal Derived Factor 1 (SDF-1)

   • Chemokines
   • Has chemokine (C-X-C motif) receptor 4 (CXCR4)
     • Expressed on GnRH neurons
   • Purpose: Guides neurons across nasal region
   • Present as conc. gradient, nasal mesenchyme
     • Highest @ Cribiform Junction
   • Mutation Consequences
     • KO CXCR4 mice → Impaired GnRH cell migration

6. Neutrin-1

   • Has Deleted in Colon Cancer (DCC) Receptor
   • Present as conc. gradient, highest in forebrain
   • F: Extends caudal VNO nerves from nasal placode to POA and arcuate
     • Essentially guides GnRH nerve fibers through the forebrain to the median eminence
   • Mutation Consequences
     • GnRH neurons migrate to cerebral cortex

7. Glutamate Decarboxylase (GAD)

   • Converts Glu to GABA
   • Gain of F(x) Consequences
     • No migration of GnRH neurons from VNO
   • This works at the cribriform plate