The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse.
We generated mice carrying a loss-of-function mutation in Brn-2, a gene encoding a nervous system specific POU transcription factor, by gene targeting in embryonic stem cells. In homozygous mutant embryos, migratory precursor cells for neurons of the paraventricular nuclei (PVN) and the supraoptic nuclei (SO) of the hypothalamus die at approximately E12.5. All homozygous mutants suffered mortality within 10 days after birth, possibly because of a complete deficiency of these neurons in the hypothalamus. Although neither developmental nor histological abnormalities were observed in heterozygous mice, the levels of expression of vasopressin and oxytocin in the hypothalamus of these animals were half these of wild-type mice. These results strongly suggest that Brn-2 plays an essential role in the determination and development of the PVN and SO neuronal lineages in the hypothalamus.
Department of Cell Biology, Cancer Institute, Tokyo, Japan.
S
S
Nakai
H
H
Kawano
T
T
Yudate
M
M
Nishi
J
J
Kuno
A
A
Nagata
K
K
Jishage
H
H
Hamada
H
H
Fujii
K
K
Kawamura
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D005804:Genes, Lethal; D018095:Germ-Line Mutation; D018398:Homeodomain Proteins; D006720:Homozygote; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D050809:POU Domain Factors; D010904:Pituitary Gland, Posterior / Q000196:embryology / Q000473:pathology; D013004:Somatostatin / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D018398:Homeodomain Proteins; D050809:POU Domain Factors; D014157:Transcription Factors; C085076:transcription factor Brn-2; D013004:Somatostatin