Role of Pax-5 in the regulation of a mid-hindbrain organizer's activity

Jun ichi Funahashi, Tatsuya Okafuji, Hideyo Ohuchi, Sumihare Noji, Hideaki Tanaka, Harukazu Nakamura

Research output: Contribution to journalArticle

191 Citations (Scopus)

Abstract

The mes-metencephalic boundary (isthmus) has been suggested to act as an organizer in the development of the optic tectum. Pax-5 was cloned as a candidate for regulator of the organizing center. Isthmus-specific expression of Pax-5 and analogy with the genetic cascade in Drosophila suggest that Pax- 5 may be at a higher hierarchical position in the gene regulation cascade of tectum development. To examine this possibility, a gain-of-function experiment on Pax-5 was carried out. In ovo electroporation on E2 chick brain with the eucaryotic expression vector that encodes chick Pax-5 cDNA was used. Not only was a considerable amount of Pax-5 expressed ectopically in the transfected brain, but irregular bulging of the neuroepithelium was induced in the diencephalon and mesencephalon. At Pax-5 misexpressing sites, uptake of BrdU was increased. Histological examination of E7 transfected brain revealed that Pax-5 caused transdifferentiation of diencephalon into the tectum-like structure. In the bulges of the E7 mesencephalon, differentiation of laminar structure was repressed when compared to the normal side. In transfected embryos, En-2, Wnt-1 and Fgf8 were up-regulated ectopically, and Otx2 was down-regulated in the diencephalon to mesencephalon. Moreover, Ephrin-A2, which is expressed specifically in the tectum with a gradient highest at the caudal end, is suggested to be involved in pathfinding of the retinal fibers, and was induced in the bulges. When the mouse Fgf8 expression vector was electroporated, Pax-5 and chick Fgf8 were also induced ectopically. These results suggest that Pax-5, together with Fgf8, hold a higher position in the genetic hierarchy of the isthmus organizing center and regulate its activity.

Original languageEnglish
Pages (from-to)59-72
Number of pages14
JournalDevelopment Growth and Differentiation
Volume41
Issue number1
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Diencephalon
Rhombencephalon
Mesencephalon
Ephrin-A2
Brain
Gene Order
Electroporation
Superior Colliculi
Bromodeoxyuridine
Drosophila
Embryonic Structures
Complementary DNA

Keywords

  • Chick
  • Fgf8
  • Isthmus
  • Pax-5
  • Tectum

ASJC Scopus subject areas

  • Anatomy
  • Developmental Biology
  • Cell Biology

Cite this

Role of Pax-5 in the regulation of a mid-hindbrain organizer's activity. / Funahashi, Jun ichi; Okafuji, Tatsuya; Ohuchi, Hideyo; Noji, Sumihare; Tanaka, Hideaki; Nakamura, Harukazu.

In: Development Growth and Differentiation, Vol. 41, No. 1, 1999, p. 59-72.

Research output: Contribution to journalArticle

Funahashi, Jun ichi ; Okafuji, Tatsuya ; Ohuchi, Hideyo ; Noji, Sumihare ; Tanaka, Hideaki ; Nakamura, Harukazu. / Role of Pax-5 in the regulation of a mid-hindbrain organizer's activity. In: Development Growth and Differentiation. 1999 ; Vol. 41, No. 1. pp. 59-72.
@article{9be18ba92efe449aa5e1ed652d79a166,
title = "Role of Pax-5 in the regulation of a mid-hindbrain organizer's activity",
abstract = "The mes-metencephalic boundary (isthmus) has been suggested to act as an organizer in the development of the optic tectum. Pax-5 was cloned as a candidate for regulator of the organizing center. Isthmus-specific expression of Pax-5 and analogy with the genetic cascade in Drosophila suggest that Pax- 5 may be at a higher hierarchical position in the gene regulation cascade of tectum development. To examine this possibility, a gain-of-function experiment on Pax-5 was carried out. In ovo electroporation on E2 chick brain with the eucaryotic expression vector that encodes chick Pax-5 cDNA was used. Not only was a considerable amount of Pax-5 expressed ectopically in the transfected brain, but irregular bulging of the neuroepithelium was induced in the diencephalon and mesencephalon. At Pax-5 misexpressing sites, uptake of BrdU was increased. Histological examination of E7 transfected brain revealed that Pax-5 caused transdifferentiation of diencephalon into the tectum-like structure. In the bulges of the E7 mesencephalon, differentiation of laminar structure was repressed when compared to the normal side. In transfected embryos, En-2, Wnt-1 and Fgf8 were up-regulated ectopically, and Otx2 was down-regulated in the diencephalon to mesencephalon. Moreover, Ephrin-A2, which is expressed specifically in the tectum with a gradient highest at the caudal end, is suggested to be involved in pathfinding of the retinal fibers, and was induced in the bulges. When the mouse Fgf8 expression vector was electroporated, Pax-5 and chick Fgf8 were also induced ectopically. These results suggest that Pax-5, together with Fgf8, hold a higher position in the genetic hierarchy of the isthmus organizing center and regulate its activity.",
keywords = "Chick, Fgf8, Isthmus, Pax-5, Tectum",
author = "Funahashi, {Jun ichi} and Tatsuya Okafuji and Hideyo Ohuchi and Sumihare Noji and Hideaki Tanaka and Harukazu Nakamura",
year = "1999",
doi = "10.1046/j.1440-169x.1999.00401.x",
language = "English",
volume = "41",
pages = "59--72",
journal = "Development Growth and Differentiation",
issn = "0012-1592",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Role of Pax-5 in the regulation of a mid-hindbrain organizer's activity

AU - Funahashi, Jun ichi

AU - Okafuji, Tatsuya

AU - Ohuchi, Hideyo

AU - Noji, Sumihare

AU - Tanaka, Hideaki

AU - Nakamura, Harukazu

PY - 1999

Y1 - 1999

N2 - The mes-metencephalic boundary (isthmus) has been suggested to act as an organizer in the development of the optic tectum. Pax-5 was cloned as a candidate for regulator of the organizing center. Isthmus-specific expression of Pax-5 and analogy with the genetic cascade in Drosophila suggest that Pax- 5 may be at a higher hierarchical position in the gene regulation cascade of tectum development. To examine this possibility, a gain-of-function experiment on Pax-5 was carried out. In ovo electroporation on E2 chick brain with the eucaryotic expression vector that encodes chick Pax-5 cDNA was used. Not only was a considerable amount of Pax-5 expressed ectopically in the transfected brain, but irregular bulging of the neuroepithelium was induced in the diencephalon and mesencephalon. At Pax-5 misexpressing sites, uptake of BrdU was increased. Histological examination of E7 transfected brain revealed that Pax-5 caused transdifferentiation of diencephalon into the tectum-like structure. In the bulges of the E7 mesencephalon, differentiation of laminar structure was repressed when compared to the normal side. In transfected embryos, En-2, Wnt-1 and Fgf8 were up-regulated ectopically, and Otx2 was down-regulated in the diencephalon to mesencephalon. Moreover, Ephrin-A2, which is expressed specifically in the tectum with a gradient highest at the caudal end, is suggested to be involved in pathfinding of the retinal fibers, and was induced in the bulges. When the mouse Fgf8 expression vector was electroporated, Pax-5 and chick Fgf8 were also induced ectopically. These results suggest that Pax-5, together with Fgf8, hold a higher position in the genetic hierarchy of the isthmus organizing center and regulate its activity.

AB - The mes-metencephalic boundary (isthmus) has been suggested to act as an organizer in the development of the optic tectum. Pax-5 was cloned as a candidate for regulator of the organizing center. Isthmus-specific expression of Pax-5 and analogy with the genetic cascade in Drosophila suggest that Pax- 5 may be at a higher hierarchical position in the gene regulation cascade of tectum development. To examine this possibility, a gain-of-function experiment on Pax-5 was carried out. In ovo electroporation on E2 chick brain with the eucaryotic expression vector that encodes chick Pax-5 cDNA was used. Not only was a considerable amount of Pax-5 expressed ectopically in the transfected brain, but irregular bulging of the neuroepithelium was induced in the diencephalon and mesencephalon. At Pax-5 misexpressing sites, uptake of BrdU was increased. Histological examination of E7 transfected brain revealed that Pax-5 caused transdifferentiation of diencephalon into the tectum-like structure. In the bulges of the E7 mesencephalon, differentiation of laminar structure was repressed when compared to the normal side. In transfected embryos, En-2, Wnt-1 and Fgf8 were up-regulated ectopically, and Otx2 was down-regulated in the diencephalon to mesencephalon. Moreover, Ephrin-A2, which is expressed specifically in the tectum with a gradient highest at the caudal end, is suggested to be involved in pathfinding of the retinal fibers, and was induced in the bulges. When the mouse Fgf8 expression vector was electroporated, Pax-5 and chick Fgf8 were also induced ectopically. These results suggest that Pax-5, together with Fgf8, hold a higher position in the genetic hierarchy of the isthmus organizing center and regulate its activity.

KW - Chick

KW - Fgf8

KW - Isthmus

KW - Pax-5

KW - Tectum

UR - http://www.scopus.com/inward/record.url?scp=0033030178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033030178&partnerID=8YFLogxK

U2 - 10.1046/j.1440-169x.1999.00401.x

DO - 10.1046/j.1440-169x.1999.00401.x

M3 - Article

C2 - 10445503

AN - SCOPUS:0033030178

VL - 41

SP - 59

EP - 72

JO - Development Growth and Differentiation

JF - Development Growth and Differentiation

SN - 0012-1592

IS - 1

ER -