The role of serine proteases and serine protease inhibitors in the migration of gonadotropin-releasing hormone neurons.
BACKGROUND
Mechanisms regulating neuronal migration during development remain largely undefined. Extracellular matrix cues, target site released factors, and components of the migratory neurons themselves are likely all coordinated in time and space directing neurons to their appropriate locations. We have studied the effects of proteases and their inhibitors on the extracellular matrix and the consequences to the migration of gonadotropin releasing hormone (GnRH) neurons in the embryonic chick. Chick GnRH neurons differentiate in the olfactory epithelium, migrate along the olfactory nerve and enter the forebrain. The accessibility of this coherent cell group make it amenable for studying protease/inhibitor roles in migratory processes.


RESULTS
Affigel blue beads were used to deliver a serine protease inhibitor, protease nexin-1 (PN-1), and a target protease, trypsin, to the olfactory epithelium coincident with initiation of GnRH neuronal migration. PN-1 inhibited neuronal migration while trypsin accelerated their transit into the CNS. Prior to initiation of migration, neither PN-1 nor trypsin altered the timing of neuronal exit. Trypsin did, however, accelerate the timing of neuronal crossing into the nerve-forebrain junction.


CONCLUSIONS
These data support the hypothesis that protease activity modulates neuronal movements across barriers. Moreover, the data suggest, for the first time, that aspects of GnRH neuronal migration may be cell autonomous but modulated by ECM alterations.
Drapkin
Paola T
PT
University of Iowa, Iowa City, IA 52242, USA. pdrapkin@blue.weeg.uiowa.edu
Monard
Denis
D
Silverman
Ann-Judith
AJ
D016564:Amyloid beta-Protein Precursor; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D005109:Extracellular Matrix / Q000737:chemistry / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009832:Olfactory Nerve / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D009865:Oocytes / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D015842:Serine Proteinase Inhibitors / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D014357:Trypsin / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D015842:Serine Proteinase Inhibitors; D007987:Gonadotropin-Releasing Hormone; D014357:Trypsin