Fezf1 is required for penetration of the basal lamina by olfactory axons to promote olfactory development.
In the development of the olfactory system, olfactory receptor neurons (ORNs) project their axons from the olfactory epithelium (OE) to the olfactory bulb (OB). The surface of the OB is covered by the central nervous system (CNS) basal lamina. To establish this connection, pioneer axons of the ORNs penetrate the CNS basal lamina at embryonic day 12.5 in mice. The importance of this penetration is highlighted by the Kallmann syndrome. However, little has been known about the molecular mechanism underlying this penetration process. Fezf1 (also called as Fez, Zfp312-like, and 3110069A13Rik) is a C2H2-type zinc-finger gene expressed in the OE and hypothalamic region in mice. In Fezf1-deficient mice, ORN axons (olfactory axons) do not reach the OB. Here we demonstrate that Fezf1-deficient olfactory axons do not penetrate the CNS basal lamina in vivo, and the penetration activity of the axons in Matrigel is impaired in vitro. Coculture experiments using the OE and OB reveal that axonal projection of ORNs is rescued in Fezf1-deficient mice in which the meninges including the CNS basal lamina are removed from the mutant OB. These data indicate that Fezf1 is required for the penetration of olfactory axons through the CNS basal lamina before they innervate the OB.
Watanabe
Yasuhito
Y
Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
Inoue
Kiyoshi
K
Okuyama-Yamamoto
Ayako
A
Nakai
Nobuhiro
N
Nakatani
Jin
J
Nibu
Ken-Ichi
K
Sato
Naoko
N
Iiboshi
Yasuhiko
Y
Yusa
Kosuke
K
Kondoh
Gen
G
Takeda
Junji
J
Terashima
Toshio
T
Takumi
Toru
T
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D001485:Basement Membrane / Q000378:metabolism* / Q000648:ultrastructure; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004338:Drug Combinations; D017403:In Situ Hybridization; D007797:Laminin / Q000378:metabolism; D008578:Meninges / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development; D009831:Olfactory Mucosa / Q000166:cytology / Q000254:growth & development; D009833:Olfactory Pathways / Q000033:anatomy & histology / Q000254:growth & development; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D012903:Smell
D015415:Biomarkers; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D007797:Laminin; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; C412364:Zfp312 protein, mouse; C059485:matrigel; D003094:Collagen