Pax-6 is involved in the specification of hindbrain motor neuron subtype

Noriko Osumi, Arisa Hirota, Hideyo Ohuchi, Masato Nakafuku, Tadahiro Iimura, Shigeru Kuratani, Michio Fujiwara, Sumihare Noji, Kazuhiro Eto

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

Pax-6 is a member of the vertebrate Pax gene family, which is structurally related to the Drosophila pair-rule gene, paired. In mammals, Pax-6 is expressed in several discrete domains of the developing CNS and has been implicated in neural development, although its precise role remains elusive. We found a novel Small eye rat strain (rSey2) with phenotypes similar to mouse and rat Small eye. Analyses of the Pax-6 gene revealed one base (C) insertion in an exon encoding the region downstream of the paired box of the Pax-6 gene, resulting in generation of truncated protein due to the frame shift. To explore the roles of Pax-6 in neural development, we searched for abnormalities in the nervous system in rSey2 homozygous embryos. rSey2/rSey2, exhibited abnormal development of motor neurons in the hindbrain. The Islet-1-positive motor neurons were generated just ventral to the Pax-6-expressing domain both in the wild-type and mutant embryos. However, two somatic motor (SM) nerves, the abducent and hypoglossal nerves, were missing in homozygous embryos, By retrograde and anterograde labeling, we found no SM-type axonogenesis (ventrally growing) in the mutant postotic hindbrain, though branchiomotor and visceral motor (BM/VM)-type axons (dorsally growing) were observed within the neural tube. To discover whether the identity of these motor neuron subtypes was changed in the mutant, we examined expression of LIM homeobox genes, Islet-1, Islet-2 and Lim-3. At the postotic levels of the hindbrain, SM neurons expressed all the three LIM genes, whereas BM/VM-type neurons were marked by Islet-1 only. In the Pax-6 mutant hindbrain, Islet-2 expression was specifically missing, which resulted in the loss of the cells harboring the postotic hindbrain SM-type LIM code (Islet-1 + Islet-2 + Lim-3). Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in the ventrolateral domain of the neural tube, was also specifically missing in the mutant hindbrain, while it remained intact in the dorsal non-overlapping domain. These results strongly suggest that Pax-6 is involved in the specification of subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2 and Wnt-7b expression.

Original languageEnglish
Pages (from-to)2961-2972
Number of pages12
JournalDevelopment
Volume124
Issue number15
Publication statusPublished - 1997
Externally publishedYes

Fingerprint

Rhombencephalon
Motor Neurons
Neural Tube
Embryonic Structures
Genes
Abducens Nerve
Hypoglossal Nerve
Nervous System Malformations
Homeobox Genes
Drosophila
Axons
Vertebrates
Mammals
Exons
Phenotype

Keywords

  • Islet-1
  • Islet-2
  • LIM homeobox genes
  • Lim-3
  • Motor neuron
  • Pax-6
  • Rat
  • Small eye
  • Wnt

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Osumi, N., Hirota, A., Ohuchi, H., Nakafuku, M., Iimura, T., Kuratani, S., ... Eto, K. (1997). Pax-6 is involved in the specification of hindbrain motor neuron subtype. Development, 124(15), 2961-2972.

Pax-6 is involved in the specification of hindbrain motor neuron subtype. / Osumi, Noriko; Hirota, Arisa; Ohuchi, Hideyo; Nakafuku, Masato; Iimura, Tadahiro; Kuratani, Shigeru; Fujiwara, Michio; Noji, Sumihare; Eto, Kazuhiro.

In: Development, Vol. 124, No. 15, 1997, p. 2961-2972.

Research output: Contribution to journalArticle

Osumi, N, Hirota, A, Ohuchi, H, Nakafuku, M, Iimura, T, Kuratani, S, Fujiwara, M, Noji, S & Eto, K 1997, 'Pax-6 is involved in the specification of hindbrain motor neuron subtype', Development, vol. 124, no. 15, pp. 2961-2972.
Osumi N, Hirota A, Ohuchi H, Nakafuku M, Iimura T, Kuratani S et al. Pax-6 is involved in the specification of hindbrain motor neuron subtype. Development. 1997;124(15):2961-2972.
Osumi, Noriko ; Hirota, Arisa ; Ohuchi, Hideyo ; Nakafuku, Masato ; Iimura, Tadahiro ; Kuratani, Shigeru ; Fujiwara, Michio ; Noji, Sumihare ; Eto, Kazuhiro. / Pax-6 is involved in the specification of hindbrain motor neuron subtype. In: Development. 1997 ; Vol. 124, No. 15. pp. 2961-2972.
@article{aad79e79078d4f3d8c7e0d72e1913578,
title = "Pax-6 is involved in the specification of hindbrain motor neuron subtype",
abstract = "Pax-6 is a member of the vertebrate Pax gene family, which is structurally related to the Drosophila pair-rule gene, paired. In mammals, Pax-6 is expressed in several discrete domains of the developing CNS and has been implicated in neural development, although its precise role remains elusive. We found a novel Small eye rat strain (rSey2) with phenotypes similar to mouse and rat Small eye. Analyses of the Pax-6 gene revealed one base (C) insertion in an exon encoding the region downstream of the paired box of the Pax-6 gene, resulting in generation of truncated protein due to the frame shift. To explore the roles of Pax-6 in neural development, we searched for abnormalities in the nervous system in rSey2 homozygous embryos. rSey2/rSey2, exhibited abnormal development of motor neurons in the hindbrain. The Islet-1-positive motor neurons were generated just ventral to the Pax-6-expressing domain both in the wild-type and mutant embryos. However, two somatic motor (SM) nerves, the abducent and hypoglossal nerves, were missing in homozygous embryos, By retrograde and anterograde labeling, we found no SM-type axonogenesis (ventrally growing) in the mutant postotic hindbrain, though branchiomotor and visceral motor (BM/VM)-type axons (dorsally growing) were observed within the neural tube. To discover whether the identity of these motor neuron subtypes was changed in the mutant, we examined expression of LIM homeobox genes, Islet-1, Islet-2 and Lim-3. At the postotic levels of the hindbrain, SM neurons expressed all the three LIM genes, whereas BM/VM-type neurons were marked by Islet-1 only. In the Pax-6 mutant hindbrain, Islet-2 expression was specifically missing, which resulted in the loss of the cells harboring the postotic hindbrain SM-type LIM code (Islet-1 + Islet-2 + Lim-3). Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in the ventrolateral domain of the neural tube, was also specifically missing in the mutant hindbrain, while it remained intact in the dorsal non-overlapping domain. These results strongly suggest that Pax-6 is involved in the specification of subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2 and Wnt-7b expression.",
keywords = "Islet-1, Islet-2, LIM homeobox genes, Lim-3, Motor neuron, Pax-6, Rat, Small eye, Wnt",
author = "Noriko Osumi and Arisa Hirota and Hideyo Ohuchi and Masato Nakafuku and Tadahiro Iimura and Shigeru Kuratani and Michio Fujiwara and Sumihare Noji and Kazuhiro Eto",
year = "1997",
language = "English",
volume = "124",
pages = "2961--2972",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "15",

}

TY - JOUR

T1 - Pax-6 is involved in the specification of hindbrain motor neuron subtype

AU - Osumi, Noriko

AU - Hirota, Arisa

AU - Ohuchi, Hideyo

AU - Nakafuku, Masato

AU - Iimura, Tadahiro

AU - Kuratani, Shigeru

AU - Fujiwara, Michio

AU - Noji, Sumihare

AU - Eto, Kazuhiro

PY - 1997

Y1 - 1997

N2 - Pax-6 is a member of the vertebrate Pax gene family, which is structurally related to the Drosophila pair-rule gene, paired. In mammals, Pax-6 is expressed in several discrete domains of the developing CNS and has been implicated in neural development, although its precise role remains elusive. We found a novel Small eye rat strain (rSey2) with phenotypes similar to mouse and rat Small eye. Analyses of the Pax-6 gene revealed one base (C) insertion in an exon encoding the region downstream of the paired box of the Pax-6 gene, resulting in generation of truncated protein due to the frame shift. To explore the roles of Pax-6 in neural development, we searched for abnormalities in the nervous system in rSey2 homozygous embryos. rSey2/rSey2, exhibited abnormal development of motor neurons in the hindbrain. The Islet-1-positive motor neurons were generated just ventral to the Pax-6-expressing domain both in the wild-type and mutant embryos. However, two somatic motor (SM) nerves, the abducent and hypoglossal nerves, were missing in homozygous embryos, By retrograde and anterograde labeling, we found no SM-type axonogenesis (ventrally growing) in the mutant postotic hindbrain, though branchiomotor and visceral motor (BM/VM)-type axons (dorsally growing) were observed within the neural tube. To discover whether the identity of these motor neuron subtypes was changed in the mutant, we examined expression of LIM homeobox genes, Islet-1, Islet-2 and Lim-3. At the postotic levels of the hindbrain, SM neurons expressed all the three LIM genes, whereas BM/VM-type neurons were marked by Islet-1 only. In the Pax-6 mutant hindbrain, Islet-2 expression was specifically missing, which resulted in the loss of the cells harboring the postotic hindbrain SM-type LIM code (Islet-1 + Islet-2 + Lim-3). Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in the ventrolateral domain of the neural tube, was also specifically missing in the mutant hindbrain, while it remained intact in the dorsal non-overlapping domain. These results strongly suggest that Pax-6 is involved in the specification of subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2 and Wnt-7b expression.

AB - Pax-6 is a member of the vertebrate Pax gene family, which is structurally related to the Drosophila pair-rule gene, paired. In mammals, Pax-6 is expressed in several discrete domains of the developing CNS and has been implicated in neural development, although its precise role remains elusive. We found a novel Small eye rat strain (rSey2) with phenotypes similar to mouse and rat Small eye. Analyses of the Pax-6 gene revealed one base (C) insertion in an exon encoding the region downstream of the paired box of the Pax-6 gene, resulting in generation of truncated protein due to the frame shift. To explore the roles of Pax-6 in neural development, we searched for abnormalities in the nervous system in rSey2 homozygous embryos. rSey2/rSey2, exhibited abnormal development of motor neurons in the hindbrain. The Islet-1-positive motor neurons were generated just ventral to the Pax-6-expressing domain both in the wild-type and mutant embryos. However, two somatic motor (SM) nerves, the abducent and hypoglossal nerves, were missing in homozygous embryos, By retrograde and anterograde labeling, we found no SM-type axonogenesis (ventrally growing) in the mutant postotic hindbrain, though branchiomotor and visceral motor (BM/VM)-type axons (dorsally growing) were observed within the neural tube. To discover whether the identity of these motor neuron subtypes was changed in the mutant, we examined expression of LIM homeobox genes, Islet-1, Islet-2 and Lim-3. At the postotic levels of the hindbrain, SM neurons expressed all the three LIM genes, whereas BM/VM-type neurons were marked by Islet-1 only. In the Pax-6 mutant hindbrain, Islet-2 expression was specifically missing, which resulted in the loss of the cells harboring the postotic hindbrain SM-type LIM code (Islet-1 + Islet-2 + Lim-3). Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in the ventrolateral domain of the neural tube, was also specifically missing in the mutant hindbrain, while it remained intact in the dorsal non-overlapping domain. These results strongly suggest that Pax-6 is involved in the specification of subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2 and Wnt-7b expression.

KW - Islet-1

KW - Islet-2

KW - LIM homeobox genes

KW - Lim-3

KW - Motor neuron

KW - Pax-6

KW - Rat

KW - Small eye

KW - Wnt

UR - http://www.scopus.com/inward/record.url?scp=0030818548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030818548&partnerID=8YFLogxK

M3 - Article

C2 - 9247338

AN - SCOPUS:0030818548

VL - 124

SP - 2961

EP - 2972

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 15

ER -