FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate

Aimin Liu, Kasia Losos, Alexandra L. Joyner

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

The mid/hindbrain junction region, which expresses Fgf8, can act as an organizer to transform caudal forebrain or hindbrain tissue into midbrain or cerebellar structures, respectively. FGF8-soaked beads placed in the chick forebrain can similarly induce ectopic expression of mid/hindbrain genes and development of midbrain structures. In contrast, ectopic expression of Fgf8a in the mouse midbrain and caudal forebrain using a Wnt1 regulatory element produced no apparent patterning defects in the embryos examined. We show here that FGF8b-soaked beads can not only induce expression of the mid/hindbrain genes En1, En2 and Pax5 in mouse embryonic day 9.5 (E9.5) caudal forebrain explants, but also can induce the hindbrain gene Gbx2 and alter the expression of Wnt1 in both midbrain and caudal forebrain explants. We also show that FGF8b-soaked beads can repress Otx2 in midbrain explants. Furthermore, Wnt1-Fgf8b transgenic embryos in which the same Wnt1 regulatory element is used to express Fgf8b, have ectopic expression of En1, En2, Pax5 and Gbx2 in the dorsal hindbrain and spinal cord at E10.5, as well as exencephaly and abnormal spinal cord morphology. More strikingly, Fgf8b expression in more rostral brain regions appears to transform the midbrain and caudal forebrain into an anterior hindbrain fate through expansion of the Gbx2 domain and repression of Otx2 as early as the 7-somite stage. These findings suggest that normal Fgf8 expression in the anterior hindbrain not only functions to maintain development of the entire mid/hindbrain by regulating genes like En1, En2 and Pax-5, but also might function to maintain a metencephalic identity by regulating Gbx2 and Otx2 expression.

Original languageEnglish (US)
Pages (from-to)4827-4838
Number of pages12
JournalDevelopment
Volume126
Issue number21
StatePublished - Nov 1999

Fingerprint

Rhombencephalon
Prosencephalon
Mesencephalon
Brain
Genes
Spinal Cord
Embryonic Structures
Somites
Neural Tube Defects

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Cell Biology

Cite this

Liu, Aimin ; Losos, Kasia ; Joyner, Alexandra L. / FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. In: Development. 1999 ; Vol. 126, No. 21. pp. 4827-4838.
@article{0d652229b51a482e84adc6e65d1cddc9,
title = "FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate",
abstract = "The mid/hindbrain junction region, which expresses Fgf8, can act as an organizer to transform caudal forebrain or hindbrain tissue into midbrain or cerebellar structures, respectively. FGF8-soaked beads placed in the chick forebrain can similarly induce ectopic expression of mid/hindbrain genes and development of midbrain structures. In contrast, ectopic expression of Fgf8a in the mouse midbrain and caudal forebrain using a Wnt1 regulatory element produced no apparent patterning defects in the embryos examined. We show here that FGF8b-soaked beads can not only induce expression of the mid/hindbrain genes En1, En2 and Pax5 in mouse embryonic day 9.5 (E9.5) caudal forebrain explants, but also can induce the hindbrain gene Gbx2 and alter the expression of Wnt1 in both midbrain and caudal forebrain explants. We also show that FGF8b-soaked beads can repress Otx2 in midbrain explants. Furthermore, Wnt1-Fgf8b transgenic embryos in which the same Wnt1 regulatory element is used to express Fgf8b, have ectopic expression of En1, En2, Pax5 and Gbx2 in the dorsal hindbrain and spinal cord at E10.5, as well as exencephaly and abnormal spinal cord morphology. More strikingly, Fgf8b expression in more rostral brain regions appears to transform the midbrain and caudal forebrain into an anterior hindbrain fate through expansion of the Gbx2 domain and repression of Otx2 as early as the 7-somite stage. These findings suggest that normal Fgf8 expression in the anterior hindbrain not only functions to maintain development of the entire mid/hindbrain by regulating genes like En1, En2 and Pax-5, but also might function to maintain a metencephalic identity by regulating Gbx2 and Otx2 expression.",
author = "Aimin Liu and Kasia Losos and Joyner, {Alexandra L.}",
year = "1999",
month = "11",
language = "English (US)",
volume = "126",
pages = "4827--4838",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "21",

}

FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. / Liu, Aimin; Losos, Kasia; Joyner, Alexandra L.

In: Development, Vol. 126, No. 21, 11.1999, p. 4827-4838.

Research output: Contribution to journalArticle

TY - JOUR

T1 - FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate

AU - Liu, Aimin

AU - Losos, Kasia

AU - Joyner, Alexandra L.

PY - 1999/11

Y1 - 1999/11

N2 - The mid/hindbrain junction region, which expresses Fgf8, can act as an organizer to transform caudal forebrain or hindbrain tissue into midbrain or cerebellar structures, respectively. FGF8-soaked beads placed in the chick forebrain can similarly induce ectopic expression of mid/hindbrain genes and development of midbrain structures. In contrast, ectopic expression of Fgf8a in the mouse midbrain and caudal forebrain using a Wnt1 regulatory element produced no apparent patterning defects in the embryos examined. We show here that FGF8b-soaked beads can not only induce expression of the mid/hindbrain genes En1, En2 and Pax5 in mouse embryonic day 9.5 (E9.5) caudal forebrain explants, but also can induce the hindbrain gene Gbx2 and alter the expression of Wnt1 in both midbrain and caudal forebrain explants. We also show that FGF8b-soaked beads can repress Otx2 in midbrain explants. Furthermore, Wnt1-Fgf8b transgenic embryos in which the same Wnt1 regulatory element is used to express Fgf8b, have ectopic expression of En1, En2, Pax5 and Gbx2 in the dorsal hindbrain and spinal cord at E10.5, as well as exencephaly and abnormal spinal cord morphology. More strikingly, Fgf8b expression in more rostral brain regions appears to transform the midbrain and caudal forebrain into an anterior hindbrain fate through expansion of the Gbx2 domain and repression of Otx2 as early as the 7-somite stage. These findings suggest that normal Fgf8 expression in the anterior hindbrain not only functions to maintain development of the entire mid/hindbrain by regulating genes like En1, En2 and Pax-5, but also might function to maintain a metencephalic identity by regulating Gbx2 and Otx2 expression.

AB - The mid/hindbrain junction region, which expresses Fgf8, can act as an organizer to transform caudal forebrain or hindbrain tissue into midbrain or cerebellar structures, respectively. FGF8-soaked beads placed in the chick forebrain can similarly induce ectopic expression of mid/hindbrain genes and development of midbrain structures. In contrast, ectopic expression of Fgf8a in the mouse midbrain and caudal forebrain using a Wnt1 regulatory element produced no apparent patterning defects in the embryos examined. We show here that FGF8b-soaked beads can not only induce expression of the mid/hindbrain genes En1, En2 and Pax5 in mouse embryonic day 9.5 (E9.5) caudal forebrain explants, but also can induce the hindbrain gene Gbx2 and alter the expression of Wnt1 in both midbrain and caudal forebrain explants. We also show that FGF8b-soaked beads can repress Otx2 in midbrain explants. Furthermore, Wnt1-Fgf8b transgenic embryos in which the same Wnt1 regulatory element is used to express Fgf8b, have ectopic expression of En1, En2, Pax5 and Gbx2 in the dorsal hindbrain and spinal cord at E10.5, as well as exencephaly and abnormal spinal cord morphology. More strikingly, Fgf8b expression in more rostral brain regions appears to transform the midbrain and caudal forebrain into an anterior hindbrain fate through expansion of the Gbx2 domain and repression of Otx2 as early as the 7-somite stage. These findings suggest that normal Fgf8 expression in the anterior hindbrain not only functions to maintain development of the entire mid/hindbrain by regulating genes like En1, En2 and Pax-5, but also might function to maintain a metencephalic identity by regulating Gbx2 and Otx2 expression.

UR - http://www.scopus.com/inward/record.url?scp=0032708854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032708854&partnerID=8YFLogxK

M3 - Article

C2 - 10518499

AN - SCOPUS:0032708854

VL - 126

SP - 4827

EP - 4838

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 21

ER -